Phenotypic Abnormality (PA): Abnormality of limb bone

---

Root: HP Hierarchy (human phenotype with 3 sub-ontologies PA, MI, ON)

Shortest distance to current term (+ for parents, - for children)	HP term [HP ID] <#Children>	(#SF|#FA)	#Supra-domain (Single|Duplex|Triple)
+ + 2:	Phenotypic abnormality [HP:0000118] <25>
+ 1:	Abnormality of the skeletal system [HP:0000924] <7>	(88|98)	(93|55|34)
+ 1:	Abnormality of limbs [HP:0040064] <8>	(58|66)	(63|33|25)
0:	Abnormality of limb bone [HP:0040068] <1>	(29|32)	(33|18|20)
- 1:	Abnormality of limb bone morphology [HP:0002813] <13>	(29|32)	(32|18|20)

---

Superfamily

Superfamily domains annotated to this HP term (Not in SDHP)
Highlighted in gray are those with FDR_all>0.001

SCOP term	FDR (all)	Annotation (direct or inherited)
Notch domain	0	DIRECT
TB module/8-cys domain	0	DIRECT
CalX-like	0	DIRECT
RuvA domain 2-like	0	DIRECT
WD40 repeat-like	0.005014	INHERITED FROM: Hand polydactyly || Duplication involving bones of the feet || Foot polydactyly
SET domain	0.01587	INHERITED FROM: Radioulnar synostosis
FnI-like domain	0.02435	INHERITED FROM: Coxa vara || Abnormality of the epiphysis of the femoral head || Abnormality of the femoral neck
Hect, E3 ligase catalytic domain	0.03857	INHERITED FROM: Abnormal digit morphology
Arginase/deacetylase	0.04332	INHERITED FROM: Aplasia/hypoplasia involving bones of the lower limbs || Aplasia/Hypoplasia involving bones of the feet || Short foot
Insulin-like	0.04332	INHERITED FROM: Deviation of finger
Histone-fold	0.09	INHERITED FROM: Abnormality of the ulna || Abnormality of the radius
ARID-like	0.09	INHERITED FROM: Aplasia/Hypoplasia of the distal phalanges of the hand || Abnormal 5th finger phalanx morphology || Aplasia/Hypoplasia of the phalanges of the hand || Abnormality of the 5th toe || Aplasia/hypoplasia involving bones of the lower limbs || Aplasia/Hypoplasia of the distal phalanx of the 5th toe || Aplasia/Hypoplasia involving bones of the feet || Abnormality of the phalanges of the toes || Short finger || Short distal phalanx of finger || Aplasia/Hypoplasia of the distal phalanges of the toes || Abnormality of the phalanges of the 5th toe || Abnormality of the distal phalanx of the 5th toe || Abnormality of the femoral neck || Aplasia/Hypoplasia of the 5th toe || Abnormal distal phalanx morphology of finger || Coxa valga || Abnormality of the distal phalanges of the toes || Aplasia/hypoplasia involving bones of the hand || Aplasia/Hypoplasia of the phalanges of the 5th toe || Aplasia/Hypoplasia of fingers || Abnormality of the distal phalanx of the 5th finger || Aplasia/Hypoplasia of the distal phalanx of the 5th finger || Absent toe || Short phalanx of finger || Abnormality of the femoral neck or head region
Hemopexin-like domain	0.1399	INHERITED FROM: Metaphyseal widening
Restriction endonuclease-like	0.147	INHERITED FROM: Abnormal thumb morphology || Abnormality of the radius || Abnormality of forearm bone
Multidrug efflux transporter AcrB transmembrane domain	0.147	INHERITED FROM: Aplasia/Hypoplasia of the distal phalanges of the hand || Aplasia/Hypoplasia of the phalanges of the hand || Short finger || Short distal phalanx of finger || Abnormal distal phalanx morphology of finger || Short phalanx of finger
BRK domain-like	0.147	INHERITED FROM: Aplasia/hypoplasia involving bones of the lower limbs
vWA-like	0.1655	INHERITED FROM: Increased laxity of fingers || Long toe || Finger joint hypermobility
HLH, helix-loop-helix DNA-binding domain	0.2012	INHERITED FROM: Abnormality of the phalanges of the 2nd finger
Metalloproteases ("zincins"), catalytic domain	0.2054	INHERITED FROM: Broad metacarpals
N-terminal nucleophile aminohydrolases (Ntn hydrolases)	0.2077	INHERITED FROM: Finger swelling
PGBD-like	0.2077	INHERITED FROM: Metaphyseal widening
Cystine-knot cytokines	0.2683	INHERITED FROM: Tarsal synostosis || Abnormality of the middle phalanx of the 5th finger || Abnormal middle phalanx morphology of the hand || Aplasia/Hypoplasia of the middle phalanges of the hand
Concanavalin A-like lectins/glucanases	0.299	INHERITED FROM: Abnormality of femoral epiphysis || Abnormality of lower limb epiphysis morphology
GroEL equatorial domain-like	0.3043	INHERITED FROM: Hand polydactyly || Polydactyly || Postaxial polydactyly || Postaxial hand polydactyly || Finger syndactyly || Duplication of phalanx of hand
p53-like transcription factors	0.4783	INHERITED FROM: Absent hand
HMG-box	0.4799	INHERITED FROM: Aplasia/Hypoplasia of the distal phalanx of the 5th toe || Abnormality of the phalanges of the 5th toe || Abnormality of the distal phalanx of the 5th toe || Aplasia/Hypoplasia of the phalanges of the 5th toe || Abnormality of the distal phalanx of the 5th finger || Aplasia/Hypoplasia of the distal phalanx of the 5th finger
Immunoglobulin	0.7796	INHERITED FROM: Short middle phalanx of toe || Abnormality of the middle phalanges of the toes
Voltage-gated potassium channels	0.9367	INHERITED FROM: Tibial torsion
Class II aaRS and biotin synthetases	0.9912	INHERITED FROM: Hammertoe

---

Family

Family domains annotated to this HP term (Not in SDHP)
Highlighted in gray are those with FDR_all>0.001

SCOP term	FDR (all)	Annotation (direct or inherited)
CalX-beta domain	0	DIRECT
Proteasome subunits	0	DIRECT
Notch domain	0	DIRECT
XPF/Rad1/Mus81 nuclease	0	DIRECT
Histone deacetylase, HDAC	0	DIRECT
Exostosin	0	DIRECT
TB module/8-cys domain	0	DIRECT
Actin/HSP70	0.0001822	DIRECT
Erythroid transcription factor GATA-1	0.001559	INHERITED FROM: Abnormality of finger || Finger clinodactyly || Abnormal digit morphology || Brachydactyly || Clinodactyly of the 5th finger
Transforming growth factor (TGF)-beta	0.006726	INHERITED FROM: Short middle phalanx of finger || Abnormal middle phalanx morphology of the hand || Aplasia/Hypoplasia of the middle phalanges of the hand
VWC domain	0.01625	INHERITED FROM: Slender finger || Long fingers
Hect, E3 ligase catalytic domain	0.02554	INHERITED FROM: Abnormal digit morphology
ZZ domain	0.02999	INHERITED FROM: Syndactyly || Clinodactyly
Insulin-like	0.02999	INHERITED FROM: Deviation of finger || Clinodactyly
PHD domain	0.03542	INHERITED FROM: Radioulnar synostosis
Integrin A (or I) domain	0.05523	INHERITED FROM: Increased laxity of fingers || Long toe || Abnormal phalangeal joint morphology of the hand || Adducted thumb || Finger joint hypermobility
ARID domain	0.06767	INHERITED FROM: Aplasia/hypoplasia involving bones of the upper limbs || Aplasia/Hypoplasia of the distal phalanges of the hand || Abnormal 5th finger phalanx morphology || Aplasia/Hypoplasia of the phalanges of the hand || Abnormality of the 5th toe || Aplasia/hypoplasia involving bones of the lower limbs || Aplasia/Hypoplasia of the distal phalanx of the 5th toe || Aplasia/Hypoplasia involving bones of the feet || Abnormality of the phalanges of the toes || Short finger || Short distal phalanx of finger || Aplasia/Hypoplasia of the distal phalanges of the toes || Abnormality of the phalanges of the 5th toe || Abnormality of the distal phalanx of the 5th toe || Abnormality of the femoral neck || Aplasia/Hypoplasia of the 5th toe || Abnormal distal phalanx morphology of finger || Coxa valga || Short digit || Abnormality of the distal phalanges of the toes || Aplasia/hypoplasia involving bones of the hand || Aplasia/Hypoplasia of the phalanges of the 5th toe || Aplasia/Hypoplasia of fingers || Abnormality of the distal phalanx of the 5th finger || Aplasia/Hypoplasia of the distal phalanx of the 5th finger || Absent toe || Short phalanx of finger || Abnormality of the femoral neck or head region
Growth factor receptor domain	0.07312	INHERITED FROM: Bowing of the arm
Fibronectin type II module	0.08015	INHERITED FROM: Abnormality of the metaphysis
Hemopexin-like domain	0.1079	INHERITED FROM: Metaphyseal widening || Abnormality of the femoral neck
BRK domain-like	0.1163	INHERITED FROM: Aplasia/hypoplasia involving bones of the lower limbs || Aplasia/hypoplasia involving bones of the hand
TSP-1 type 1 repeat	0.1297	INHERITED FROM: Abnormality of femoral epiphysis || Abnormality of the epiphysis of the femoral head
HLH, helix-loop-helix DNA-binding domain	0.1519	INHERITED FROM: Abnormality of the phalanges of the 2nd finger
Matrix metalloproteases, catalytic domain	0.1681	INHERITED FROM: Metaphyseal widening
MMP N-terminal domain	0.1681	INHERITED FROM: Metaphyseal widening
Tetratricopeptide repeat (TPR)	0.2147	INHERITED FROM: Postaxial polydactyly
Homeodomain	0.2465	INHERITED FROM: Aplasia/Hypoplasia of the 2nd finger
RecA protein-like (ATPase-domain)	0.2883	INHERITED FROM: Clubbing || Abnormality of thumb phalanx || Abnormal morphology of ulna || Triphalangeal thumb || Clubbing of toes || Aplasia/Hypoplasia of the ulna || Hypoplasia of the ulna || Toe syndactyly || Aplasia/Hypoplasia of the radius || Forearm undergrowth || Triangular shaped phalanges of the hand || Abnormal forearm bone morphology
Classic zinc finger, C2H2	0.2887	INHERITED FROM: Hand polydactyly
HMG-box	0.4197	INHERITED FROM: Aplasia/Hypoplasia of the distal phalanx of the 5th toe || Abnormality of the phalanges of the 5th toe || Abnormality of the distal phalanx of the 5th toe || Aplasia/Hypoplasia of the phalanges of the 5th toe || Abnormality of the distal phalanx of the 5th finger || Aplasia/Hypoplasia of the distal phalanx of the 5th finger
I set domains	0.4922	INHERITED FROM: Short middle phalanx of toe || Aplasia involving bones of the upper limbs || Aplasia involving bones of the extremities || Abnormality of the tarsal bones || Abnormality of the middle phalanges of the toes || Aplasia of the phalanges of the hand
Class II aminoacyl-tRNA synthetase (aaRS)-like, catalytic domain	0.9598	INHERITED FROM: Hammertoe

---

Supra-domain (including individual superfamily)

Supra-domains annotated to this HP term (Not in SPHO)
Highlighted in gray are those with FDR>0.001

Supra-domain (Single)	FDR (all)	Annotation (direct or inherited)
CalX-like	0	DIRECT
Notch domain	0	DIRECT
RuvA domain 2-like	0	DIRECT
TB module/8-cys domain	0	DIRECT
Protein kinase-like (PK-like)	0.0007308	DIRECT
WD40 repeat-like	0.003052	INHERITED FROM: Duplication involving bones of the feet || Foot polydactyly || Abnormality of limb bone morphology || Hand polydactyly
SET domain	0.01058	INHERITED FROM: Radioulnar synostosis
FnI-like domain	0.01681	INHERITED FROM: Abnormality of the femoral neck or head region || Abnormality of the epiphysis of the femoral head || Coxa vara || Abnormality of the femoral neck
Hect, E3 ligase catalytic domain	0.02769	INHERITED FROM: Abnormal digit morphology
Insulin-like	0.03137	INHERITED FROM: Clinodactyly || Deviation of finger
Arginase/deacetylase	0.03137	INHERITED FROM: Aplasia/hypoplasia involving bones of the lower limbs || Aplasia/hypoplasia involving bones of the hand || Aplasia/Hypoplasia involving bones of the feet || Short foot
Histone-fold	0.07	INHERITED FROM: Abnormality of the ulna || Abnormality of forearm bone || Abnormality of the radius
ARID-like	0.07	INHERITED FROM: Aplasia/hypoplasia involving bones of the lower limbs || Abnormal distal phalanx morphology of finger || Aplasia/Hypoplasia of fingers || Aplasia/Hypoplasia of the patella || Aplasia/hypoplasia involving bones of the hand || Abnormality of the distal phalanx of the 5th finger || Aplasia/Hypoplasia of the distal phalanx of the 5th finger || Aplasia/Hypoplasia of the phalanges of the 5th toe || Short digit || Short finger || Abnormality of the femoral neck or head region || Aplasia/hypoplasia involving bones of the upper limbs || Short distal phalanx of finger || Abnormality of the phalanges of the toes || Coxa valga || Aplasia/Hypoplasia involving bones of the feet || Abnormality of the distal phalanges of the toes || Aplasia/Hypoplasia of the distal phalanges of the hand || Abnormal 5th finger phalanx morphology || Aplasia/Hypoplasia of the 5th toe || Abnormality of the femoral neck || Short phalanx of finger || Aplasia/Hypoplasia of the distal phalanges of the toes || Abnormality of the phalanges of the 5th toe || Abnormality of the distal phalanx of the 5th toe || Aplasia/Hypoplasia of the phalanges of the hand || Aplasia/Hypoplasia of the distal phalanx of the 5th toe || Absent toe || Abnormality of the 5th toe
TPR-like	0.09967	INHERITED FROM: Postaxial polydactyly
Nucleotide-diphospho-sugar transferases	0.1074	INHERITED FROM: Abnormality of the radius
Hemopexin-like domain	0.1135	INHERITED FROM: Metaphyseal widening || Abnormality of the femoral neck
BRK domain-like	0.1198	INHERITED FROM: Aplasia/hypoplasia involving bones of the lower limbs || Aplasia/hypoplasia involving bones of the hand
Multidrug efflux transporter AcrB transmembrane domain	0.1198	INHERITED FROM: Abnormal distal phalanx morphology of finger || Aplasia/Hypoplasia of fingers || Short finger || Short distal phalanx of finger || Aplasia/Hypoplasia of the distal phalanges of the hand || Short phalanx of finger || Aplasia/Hypoplasia of the phalanges of the hand
Restriction endonuclease-like	0.1198	INHERITED FROM: Abnormality of forearm bone || Abnormality of the radius || Abnormal upper limb bone morphology || Abnormal thumb morphology
vWA-like	0.1359	INHERITED FROM: Increased laxity of fingers || Slender finger || Finger joint hypermobility || Long toe
HLH, helix-loop-helix DNA-binding domain	0.1684	INHERITED FROM: Abnormality of the phalanges of the 2nd finger
Metalloproteases ("zincins"), catalytic domain	0.1722	INHERITED FROM: Broad metacarpals
N-terminal nucleophile aminohydrolases (Ntn hydrolases)	0.1744	INHERITED FROM: Finger swelling
PGBD-like	0.1744	INHERITED FROM: Metaphyseal widening
Cystine-knot cytokines	0.2303	INHERITED FROM: Tarsal synostosis || Abnormality of the middle phalanx of the 5th finger || Aplasia/Hypoplasia of the middle phalanges of the hand || Synostosis involving bones of the feet || Abnormal middle phalanx morphology of the hand || Short hallux || Abnormal 5th finger phalanx morphology || Aplasia/Hypoplasia of the hallux
Concanavalin A-like lectins/glucanases	0.2592	INHERITED FROM: Abnormality of lower limb epiphysis morphology || Abnormality of femoral epiphysis
GroEL equatorial domain-like	0.2643	INHERITED FROM: Postaxial hand polydactyly || Finger syndactyly || Polydactyly || Duplication of phalanx of hand || Postaxial polydactyly || Hand polydactyly
p53-like transcription factors	0.4344	INHERITED FROM: Absent hand
HMG-box	0.4361	INHERITED FROM: Abnormality of the distal phalanx of the 5th finger || Aplasia/Hypoplasia of the distal phalanx of the 5th finger || Aplasia/Hypoplasia of the phalanges of the 5th toe || Abnormality of the phalanges of the 5th toe || Abnormality of the distal phalanx of the 5th toe || Aplasia/Hypoplasia of the distal phalanx of the 5th toe
Cysteine proteinases	0.7367	INHERITED FROM: Clinodactyly of the 2nd toe
Immunoglobulin	0.7433	INHERITED FROM: Short middle phalanx of toe || Abnormality of the middle phalanges of the toes
Voltage-gated potassium channels	0.9101	INHERITED FROM: Tibial torsion
Class II aaRS and biotin synthetases	0.9699	INHERITED FROM: Hammertoe

Supra-domains annotated to this HP term (Not in SPHO)
Highlighted in gray are those with FDR>0.001

Supra-domain (Duplex) in N- to C-terminal order	FDR (all)	Annotation (direct or inherited)
57581,57196 57581 - TB module/8-cys domain 57196 - EGF/Laminin	0	DIRECT
52980,47781 52980 - Restriction endonuclease-like 47781 - RuvA domain 2-like	0	DIRECT
57196,57581 57196 - EGF/Laminin 57581 - TB module/8-cys domain	0	DIRECT
57196,90193 57196 - EGF/Laminin 90193 - Notch domain	0	DIRECT
141072,141072 141072 - CalX-like 141072 - CalX-like	0	DIRECT
57184,57581 57184 - Growth factor receptor domain 57581 - TB module/8-cys domain	0	DIRECT
57581,57184 57581 - TB module/8-cys domain 57184 - Growth factor receptor domain	0	DIRECT
57196,57184 57196 - EGF/Laminin 57184 - Growth factor receptor domain	0.002064	INHERITED FROM: Short finger || Short phalanx of finger || Brachydactyly || Absent toe
57184,57184 57184 - Growth factor receptor domain 57184 - Growth factor receptor domain	0.04223	INHERITED FROM: Abnormal digit morphology || Brachydactyly
81296,81296 81296 - E set domains 81296 - E set domains	0.07	INHERITED FROM: Abnormality of the ulna || Abnormality of forearm bone || Abnormality of the radius || Aplasia/Hypoplasia involving the metacarpal bones || Abnormality of fibula morphology || Aplasia/Hypoplasia of the fibula || Abnormal metacarpal morphology
50729,50729 50729 - PH domain-like 50729 - PH domain-like	0.07858	INHERITED FROM: Camptodactyly of finger
53300,53300 53300 - vWA-like 53300 - vWA-like	0.1198	INHERITED FROM: Increased laxity of fingers || Adducted thumb || Slender finger || Finger joint hypermobility || Long toe || Abnormal thumb morphology || Abnormal phalangeal joint morphology of the hand || Camptodactyly of finger
103575,48726 103575 - Plexin repeat 48726 - Immunoglobulin	0.1198	INHERITED FROM: Abnormal thumb morphology
47090,55486 47090 - PGBD-like 55486 - Metalloproteases ("zincins"), catalytic domain	0.1744	INHERITED FROM: Metaphyseal widening
57903,57903 57903 - FYVE/PHD zinc finger 57903 - FYVE/PHD zinc finger	0.1744	INHERITED FROM: Short digit || Short phalanx of finger || Aplasia/Hypoplasia of the phalanges of the hand
48452,48452 48452 - TPR-like 48452 - TPR-like	0.3489	INHERITED FROM: Postaxial polydactyly
48726,48726 48726 - Immunoglobulin 48726 - Immunoglobulin	0.5242	INHERITED FROM: Abnormality of the tarsal bones || Short middle phalanx of toe || Abnormality of the middle phalanges of the toes
57667,57667 57667 - beta-beta-alpha zinc fingers 57667 - beta-beta-alpha zinc fingers	0.6186	INHERITED FROM: Hand polydactyly

Supra-domains annotated to this HP term (Not in SPHO)
Highlighted in gray are those with FDR>0.001

Supra-domain (Triple) in N- to C-terminal order	FDR (all)	Annotation (direct or inherited)
57196,57581,57196 57196 - EGF/Laminin 57581 - TB module/8-cys domain 57196 - EGF/Laminin	0	DIRECT
57184,57581,57196 57184 - Growth factor receptor domain 57581 - TB module/8-cys domain 57196 - EGF/Laminin	0	DIRECT
57196,57196,57581 57196 - EGF/Laminin 57196 - EGF/Laminin 57581 - TB module/8-cys domain	0	DIRECT
57184,57184,57196 57184 - Growth factor receptor domain 57184 - Growth factor receptor domain 57196 - EGF/Laminin	0	DIRECT
141072,141072,141072 141072 - CalX-like 141072 - CalX-like 141072 - CalX-like	0	DIRECT
57196,57184,57184 57196 - EGF/Laminin 57184 - Growth factor receptor domain 57184 - Growth factor receptor domain	0	DIRECT
57184,57184,57184 57184 - Growth factor receptor domain 57184 - Growth factor receptor domain 57184 - Growth factor receptor domain	0	DIRECT
57581,57196,57581 57581 - TB module/8-cys domain 57196 - EGF/Laminin 57581 - TB module/8-cys domain	0	DIRECT
57184,57184,57581 57184 - Growth factor receptor domain 57184 - Growth factor receptor domain 57581 - TB module/8-cys domain	0	DIRECT
57581,57196,57196 57581 - TB module/8-cys domain 57196 - EGF/Laminin 57196 - EGF/Laminin	0	DIRECT
57196,57196,90193 57196 - EGF/Laminin 57196 - EGF/Laminin 90193 - Notch domain	0	DIRECT
57184,57581,57184 57184 - Growth factor receptor domain 57581 - TB module/8-cys domain 57184 - Growth factor receptor domain	0	DIRECT
57196,57581,57184 57196 - EGF/Laminin 57581 - TB module/8-cys domain 57184 - Growth factor receptor domain	0	DIRECT
57184,57196,57184 57184 - Growth factor receptor domain 57196 - EGF/Laminin 57184 - Growth factor receptor domain	0	DIRECT
57581,57184,57581 57581 - TB module/8-cys domain 57184 - Growth factor receptor domain 57581 - TB module/8-cys domain	0	DIRECT
57196,57196,57184 57196 - EGF/Laminin 57196 - EGF/Laminin 57184 - Growth factor receptor domain	0.003882	INHERITED FROM: Short finger || Abnormality of limb bone morphology || Short phalanx of finger || Brachydactyly || Absent toe
81296,81296,81296 81296 - E set domains 81296 - E set domains 81296 - E set domains	0.07	INHERITED FROM: Abnormality of the ulna || Abnormality of forearm bone || Abnormality of the radius || Aplasia/Hypoplasia involving the metacarpal bones || Abnormality of fibula morphology || Aplasia/Hypoplasia of the fibula || Abnormal metacarpal morphology
48726,48726,48726 48726 - Immunoglobulin 48726 - Immunoglobulin 48726 - Immunoglobulin	0.07262	INHERITED FROM: Abnormality of the tarsal bones || Short middle phalanx of toe || Rocker bottom foot || Abnormality of the middle phalanges of the toes
101912,103575,48726 101912 - Sema domain 103575 - Plexin repeat 48726 - Immunoglobulin	0.1198	INHERITED FROM: Abnormal thumb morphology
52540,52540,52540 52540 - P-loop containing nucleoside triphosphate hydrolases 52540 - P-loop containing nucleoside triphosphate hydrolases 52540 - P-loop containing nucleoside triphosphate hydrolases	0.2976	INHERITED FROM: Clubbing of fingers || Clubbing || Abnormal fingertip morphology