Phenotypic Abnormality (PA): Abnormality of the lower limb 

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>	#Domains (Superfamily|Family)	#Supra-domain (Single|Duplex|Triple)
+ + 2:	Phenotypic abnormality [HP:0000118] <25>
+ 1:	Abnormality of limbs [HP:0040064] <8>	(58|66)	(63|33|25)
0:	Abnormality of the lower limb [HP:0002814] <17>	(31|34)	(35|15|13)
- 1:	Abnormality of the foot [HP:0001760] <30>	(20|24)	(21|13|10)
- 1:	Abnormal lower limb bone morphology [HP:0040069] <10>	(11|9)	(12|5|6)
- 1:	Abnormality of the musculature of the lower limbs [HP:0001437] <6>	(3|3)	(5|2|2)
- 1:	Abnormality of lower limb joint [HP:0100491] <5>	(10|13)	(11|2|1)
- 1:	Abnormality of lower limb epiphysis morphology [HP:0006500] <4>	(2|1)	(2|0|0)
- 1:	Abnormality of the calf [HP:0002981] <3>	(1|0)	(1|1|1)
- 1:	Abnormality of lower-limb metaphyses [HP:0006490] <2>	(0|0)	(0|0|0)
- 1:	Areflexia of lower limbs [HP:0002522] <2>	(1|0)	(1|0|0)
- 1:	Distal lower limb muscle weakness [HP:0009053] <2>	(1|0)	(1|0|0)
- 1:	Hyporeflexia of lower limbs [HP:0002600] <2>	(1|0)	(1|0|0)
- 1:	Lower limb asymmetry [HP:0100559] <2>	(0|0)	(0|0|0)
- 1:	Externally rotated/abducted legs [HP:0003783] <1>	(0|0)	(0|0|0)
- 1:	Hypertrophy of the lower limb [HP:0010496] <1>	(0|0)	(0|0|0)
- 1:	Pedal edema [HP:0010741] <1>	(0|0)	(0|0|0)
- 1:	Amniotic constriction rings of legs [HP:0010495]	(0|0)	(0|0|0)
- 1:	Rickets of the lower limbs [HP:0006463]	(0|0)	(0|0|0)
- 1:	Sirenomelia [HP:0010497]	(0|0)	(0|0|0)

Superfamily

Highlighted in gray are those with FDR_all>0.001

SCOP term	FDR (all)	Annotation (direct or inherited)
Rhodanese/Cell cycle control phosphatase	0	DIRECT
Hedgehog/intein (Hint) domain	0	DIRECT
CalX-like	0	DIRECT
RuvA domain 2-like	0	DIRECT
Hedgehog/DD-peptidase	0	DIRECT
Plakin repeat	0	DIRECT
BRK domain-like	0	DIRECT
Nucleotide-diphospho-sugar transferases	0.0205	INHERITED FROM: Abnormality of the calf musculature
Spectrin repeat	0.04286	INHERITED FROM: Achilles tendon contracture || Abnormality of the Achilles tendon
Arginase/deacetylase	0.04577	INHERITED FROM: Aplasia/Hypoplasia involving bones of the feet || Aplasia/hypoplasia involving bones of the lower limbs || Short foot
Restriction endonuclease-like	0.04577	INHERITED FROM: Abnormality of the hip joint || Hip dislocation
HMG-box	0.04918	INHERITED FROM: Aplasia/Hypoplasia of the phalanges of the 5th toe || Aplasia/Hypoplasia of the distal phalanx of the 5th toe || Abnormality of the distal phalanx of the 5th toe || Abnormality of the phalanges of the 5th toe
ARID-like	0.05619	INHERITED FROM: Aplasia/Hypoplasia involving bones of the feet || Abnormality of the distal phalanges of the toes || Abnormality of the phalanges of the toes || Aplasia/Hypoplasia of the phalanges of the 5th toe || Aplasia/Hypoplasia of the 5th toe || Abnormality of the 5th toe || Aplasia/Hypoplasia of the distal phalanx of the 5th toe || Aplasia/hypoplasia involving bones of the lower limbs || Coxa valga || Abnormality of the distal phalanx of the 5th toe || Abnormality of the phalanges of the 5th toe || Absent toe || Aplasia/Hypoplasia of the distal phalanges of the toes || Abnormality of the femoral neck or head region || Abnormality of the femoral neck || Abnormal patella morphology
Calponin-homology domain, CH-domain	0.07389	INHERITED FROM: Abnormality of the musculature of the lower limbs
SNARE fusion complex	0.1109	INHERITED FROM: Hip dislocation
Bromodomain	0.1119	INHERITED FROM: Abnormal patella morphology
Concanavalin A-like lectins/glucanases	0.132	INHERITED FROM: Abnormality of femoral epiphysis || Abnormality of lower limb epiphysis morphology
Prefoldin	0.1674	INHERITED FROM: Palmoplantar hyperkeratosis || Abnormality of the plantar skin of foot || Plantar hyperkeratosis
SET domain	0.231	INHERITED FROM: Hip dislocation
MIR domain	0.2739	INHERITED FROM: Muscle hypertrophy of the lower extremities || Abnormality of the calf musculature || Abnormality of the musculature of the lower limbs || Calf muscle hypertrophy
Intermediate filament protein, coiled coil region	0.2903	INHERITED FROM: Abnormality of the plantar skin of foot
FnI-like domain	0.3675	INHERITED FROM: Coxa vara || Abnormality of the femoral neck || Abnormality of the epiphysis of the femoral head
Class II aaRS and biotin synthetases	0.3675	INHERITED FROM: Hammertoe
Tropomyosin	0.3727	INHERITED FROM: Knee flexion contracture || Abnormality of the hip joint || Hip dislocation || Talipes equinovarus
HSP20-like chaperones	0.3727	INHERITED FROM: Areflexia of lower limbs || Distal lower limb muscle weakness || Hyporeflexia of lower limbs
S15/NS1 RNA-binding domain	0.456	INHERITED FROM: Pes cavus
Immunoglobulin	0.6992	INHERITED FROM: Short middle phalanx of toe || Abnormality of the middle phalanges of the toes
WD40 repeat-like	0.8577	INHERITED FROM: Foot polydactyly || Duplication involving bones of the feet
Cystine-knot cytokines	0.8885	INHERITED FROM: Tarsal synostosis
vWA-like	0.9213	INHERITED FROM: Increased laxity of ankles || Pes valgus || Ankle flexion contracture || Long toe
Voltage-gated potassium channels	1	INHERITED FROM: Limited knee extension || Talipes valgus || Tibial torsion

Family

Highlighted in gray are those with FDR_all>0.001

SCOP term	FDR (all)	Annotation (direct or inherited)
CalX-beta domain	0	DIRECT
Myotubularin-like phosphatases	0	DIRECT
Filamin repeat (rod domain)	0	DIRECT
BRK domain-like	0	DIRECT
XPF/Rad1/Mus81 nuclease	0	DIRECT
Histone deacetylase, HDAC	0	DIRECT
Plakin repeat	0	DIRECT
Hedgehog (development protein), N-terminal signaling domain	0	DIRECT
Exostosin	0	DIRECT
Inositol polyphosphate 5-phosphatase (IPP5)	0	DIRECT
Hedgehog C-terminal (Hog) autoprocessing domain	0	DIRECT
Histone lysine methyltransferases	0.009842	INHERITED FROM: Hip dislocation || Talipes
VWC domain	0.01924	INHERITED FROM: Abnormality of the hip joint || Hip dislocation || Talipes || Talipes equinovarus
Spectrin repeat	0.03078	INHERITED FROM: Achilles tendon contracture || Abnormality of the Achilles tendon
ZZ domain	0.03382	INHERITED FROM: Pes planus
HMG-box	0.03589	INHERITED FROM: Aplasia/Hypoplasia of the phalanges of the 5th toe || Aplasia/Hypoplasia of the distal phalanx of the 5th toe || Abnormality of the distal phalanx of the 5th toe || Abnormality of the phalanges of the 5th toe
RecA protein-like (ATPase-domain)	0.04132	INHERITED FROM: Toe syndactyly || Hip dislocation || Clubbing of toes
ARID domain	0.04225	INHERITED FROM: Aplasia/Hypoplasia involving bones of the feet || Abnormality of the distal phalanges of the toes || Abnormality of the phalanges of the toes || Aplasia/Hypoplasia of the phalanges of the 5th toe || Aplasia/Hypoplasia of the 5th toe || Abnormality of the 5th toe || Aplasia/Hypoplasia of the distal phalanx of the 5th toe || Aplasia/hypoplasia involving bones of the lower limbs || Coxa valga || Abnormality of the distal phalanx of the 5th toe || Abnormality of the phalanges of the 5th toe || Absent toe || Aplasia/Hypoplasia of the distal phalanges of the toes || Abnormality of the femoral neck or head region || Abnormality of the femoral neck || Abnormal patella morphology
Calponin-homology domain, CH-domain	0.06642	INHERITED FROM: Abnormality of the musculature of the lower limbs || Abnormality of the Achilles tendon
SNARE fusion complex	0.08849	INHERITED FROM: Abnormality of the hip joint || Hip dislocation
Bromodomain	0.1006	INHERITED FROM: Abnormal patella morphology
MIR domain	0.2357	INHERITED FROM: Muscle hypertrophy of the lower extremities || Abnormality of the calf musculature || Abnormality of the musculature of the lower limbs || Calf muscle hypertrophy
Intermediate filament protein, coiled coil region	0.2484	INHERITED FROM: Abnormality of the plantar skin of foot || Plantar hyperkeratosis
Hemopexin-like domain	0.2848	INHERITED FROM: Abnormality of the femoral neck
TSP-1 type 1 repeat	0.301	INHERITED FROM: Abnormality of femoral epiphysis || Abnormality of the epiphysis of the femoral head
Tyrosine-dependent oxidoreductases	0.3048	INHERITED FROM: Palmoplantar hyperkeratosis
Tropomyosin	0.351	INHERITED FROM: Knee flexion contracture || Abnormality of the hip joint || Hip dislocation || Talipes equinovarus
Class II aminoacyl-tRNA synthetase (aaRS)-like, catalytic domain	0.3523	INHERITED FROM: Hammertoe
LIM domain	0.409	INHERITED FROM: Abnormality of the musculature of the lower limbs
a tRNA synthase domain	0.4328	INHERITED FROM: Pes cavus
Clathrin adaptor core protein	0.4328	INHERITED FROM: Abnormality of the acetabulum || Acetabular dysplasia || Abnormality of the hip joint
I set domains	0.4494	INHERITED FROM: Abnormality of the tarsal bones || Short middle phalanx of toe || Abnormality of the middle phalanges of the toes
Myosin rod fragments	0.4755	INHERITED FROM: Hip dislocation
Integrin A (or I) domain	0.8283	INHERITED FROM: Increased laxity of ankles || Pes valgus || Ankle flexion contracture || Long toe

Supra-domain (Single|Duplex|Triple)

Supra-domain (Single)

Highlighted in gray are those with FDR>0.001

Supra-domain (Single)	FDR (all)	Annotation (direct or inherited)
Hedgehog/DD-peptidase	0	DIRECT
Hedgehog/intein (Hint) domain	0	DIRECT
BRK domain-like	0	DIRECT
RuvA domain 2-like	0	DIRECT
Rhodanese/Cell cycle control phosphatase	0	DIRECT
CalX-like	0	DIRECT
Plakin repeat	0	DIRECT
Nucleotide-diphospho-sugar transferases	0.01399	INHERITED FROM: Abnormality of the calf musculature
Spectrin repeat	0.03101	INHERITED FROM: Achilles tendon contracture || Abnormality of the musculature of the lower limbs || Abnormality of the Achilles tendon
Arginase/deacetylase	0.03339	INHERITED FROM: Aplasia/Hypoplasia involving bones of the feet || Aplasia/hypoplasia involving bones of the lower limbs || Short foot
Restriction endonuclease-like	0.03339	INHERITED FROM: Hip dislocation || Abnormality of the hip joint
Cysteine proteinases	0.03581	INHERITED FROM: Clinodactyly of the 2nd toe
HMG-box	0.03616	INHERITED FROM: Aplasia/Hypoplasia of the phalanges of the 5th toe || Aplasia/Hypoplasia of the distal phalanx of the 5th toe || Abnormality of the distal phalanx of the 5th toe || Abnormality of the phalanges of the 5th toe
ARID-like	0.04191	INHERITED FROM: Abnormal patella morphology || Aplasia/Hypoplasia of the patella || Abnormality of the femoral neck || Aplasia/Hypoplasia of the phalanges of the 5th toe || Aplasia/Hypoplasia of the distal phalanx of the 5th toe || Abnormality of the distal phalanx of the 5th toe || Abnormality of the phalanges of the 5th toe || Aplasia/Hypoplasia of the distal phalanges of the toes || Abnormality of the 5th toe || Absent toe || Abnormality of the femoral neck or head region || Abnormality of the phalanges of the toes || Aplasia/Hypoplasia involving bones of the feet || Coxa valga || Aplasia/hypoplasia involving bones of the lower limbs || Abnormality of the distal phalanges of the toes || Aplasia/Hypoplasia of the 5th toe
Calponin-homology domain, CH-domain	0.05652	INHERITED FROM: Abnormality of the musculature of the lower limbs
SNARE fusion complex	0.08753	INHERITED FROM: Hip dislocation || Abnormality of the hip joint
Bromodomain	0.08836	INHERITED FROM: Abnormal patella morphology
Concanavalin A-like lectins/glucanases	0.1064	INHERITED FROM: Abnormality of lower limb epiphysis morphology || Abnormality of femoral epiphysis
Prefoldin	0.1376	INHERITED FROM: Palmoplantar hyperkeratosis || Plantar hyperkeratosis || Abnormality of the plantar skin of foot
SET domain	0.1957	INHERITED FROM: Hip dislocation
MIR domain	0.2357	INHERITED FROM: Calf muscle hypertrophy || Abnormality of the calf musculature || Muscle hypertrophy of the lower extremities || Abnormality of the musculature of the lower limbs
Intermediate filament protein, coiled coil region	0.251	INHERITED FROM: Plantar hyperkeratosis || Abnormality of the plantar skin of foot
Hemopexin-like domain	0.2654	INHERITED FROM: Abnormality of the femoral neck
FnI-like domain	0.3249	INHERITED FROM: Abnormality of the femoral neck || Coxa vara || Abnormality of the epiphysis of the femoral head || Abnormality of the femoral neck or head region
Class II aaRS and biotin synthetases	0.3249	INHERITED FROM: Hammertoe
Tropomyosin	0.3298	INHERITED FROM: Hip dislocation || Abnormality of the hip joint || Positional foot deformity || Talipes || Knee flexion contracture || Talipes equinovarus
HSP20-like chaperones	0.3298	INHERITED FROM: Distal lower limb muscle weakness || Areflexia of lower limbs || Hyporeflexia of lower limbs
S15/NS1 RNA-binding domain	0.4121	INHERITED FROM: Pes cavus
Myosin rod fragments	0.4465	INHERITED FROM: Hip dislocation
Glucocorticoid receptor-like (DNA-binding domain)	0.6527	INHERITED FROM: Abnormality of the musculature of the lower limbs
Immunoglobulin	0.6604	INHERITED FROM: Abnormality of the middle phalanges of the toes || Short middle phalanx of toe
WD40 repeat-like	0.8258	INHERITED FROM: Duplication involving bones of the feet || Foot polydactyly
Cystine-knot cytokines	0.8586	INHERITED FROM: Aplasia/Hypoplasia of the hallux || Synostosis involving bones of the feet || Short hallux || Tarsal synostosis
vWA-like	0.8936	INHERITED FROM: Ankle flexion contracture || Pes valgus || Increased laxity of ankles || Long toe
Voltage-gated potassium channels	0.9998	INHERITED FROM: Talipes valgus || Tibial torsion || Limited knee extension

Supra-domain (Duplex) in N- to C-terminal order

Highlighted in gray are those with FDR>0.001

Supra-domain (Duplex) in N- to C-terminal order	FDR (all)	Annotation (direct or inherited)
52980,47781 52980 - Restriction endonuclease-like 47781 - RuvA domain 2-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
75399,75399 75399 - Plakin repeat 75399 - Plakin repeat	0	DIRECT
55166,51294 55166 - Hedgehog/DD-peptidase 51294 - Hedgehog/intein (Hint) domain	0	DIRECT
141072,141072 141072 - CalX-like 141072 - CalX-like	0	DIRECT
81296,81296 81296 - E set domains 81296 - E set domains	0.00531	INHERITED FROM: Abnormality of fibula morphology || Aplasia/Hypoplasia of the fibula
46579,64593 46579 - Prefoldin 64593 - Intermediate filament protein, coiled coil region	0.03339	INHERITED FROM: Palmoplantar hyperkeratosis || Plantar hyperkeratosis || Abnormality of the plantar skin of foot
53300,53300 53300 - vWA-like 53300 - vWA-like	0.08753	INHERITED FROM: Hip dislocation || Ankle flexion contracture || Abnormality of the ankles || Pes valgus || Abnormality of the hip joint || Increased laxity of ankles || Abnormality of the knee || Knee flexion contracture || Long toe || Talipes equinovarus
46966,46966 46966 - Spectrin repeat 46966 - Spectrin repeat	0.08995	INHERITED FROM: Achilles tendon contracture || Abnormality of the musculature of the lower limbs || Abnormality of the Achilles tendon
48726,48726 48726 - Immunoglobulin 48726 - Immunoglobulin	0.3166	INHERITED FROM: Abnormality of the middle phalanges of the toes || Short middle phalanx of toe || Abnormality of the tarsal bones
57716,57716 57716 - Glucocorticoid receptor-like (DNA-binding domain) 57716 - Glucocorticoid receptor-like (DNA-binding domain)	0.5185	INHERITED FROM: Abnormality of the musculature of the lower limbs
64593,64593 64593 - Intermediate filament protein, coiled coil region 64593 - Intermediate filament protein, coiled coil region	0.5526	INHERITED FROM: Abnormality of the plantar skin of foot
57196,57196 57196 - EGF/Laminin 57196 - EGF/Laminin	0.5865	INHERITED FROM: Plantar hyperkeratosis
57196,57184 57196 - EGF/Laminin 57184 - Growth factor receptor domain	0.7981	INHERITED FROM: Absent toe

Supra-domain (Triple) in N- to C-terminal order

Highlighted in gray are those with FDR>0.001

Supra-domain (Triple) in N- to C-terminal order	FDR (all)	Annotation (direct or inherited)
141072,141072,141072 141072 - CalX-like 141072 - CalX-like 141072 - CalX-like	0	DIRECT
57184,57581,57184 57184 - Growth factor receptor domain 57581 - TB module/8-cys 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
57184,57581,57196 57184 - Growth factor receptor domain 57581 - TB module/8-cys domain 57196 - EGF/Laminin	0	DIRECT
57184,57184,57581 57184 - Growth factor receptor domain 57184 - Growth factor receptor domain 57581 - TB module/8-cys 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
81296,81296,81296 81296 - E set domains 81296 - E set domains 81296 - E set domains	0.00531	INHERITED FROM: Abnormality of fibula morphology || Aplasia/Hypoplasia of the fibula
57716,57716,57716 57716 - Glucocorticoid receptor-like (DNA-binding domain) 57716 - Glucocorticoid receptor-like (DNA-binding domain) 57716 - Glucocorticoid receptor-like (DNA-binding domain)	0.1376	INHERITED FROM: Abnormality of the musculature of the lower limbs
46966,46966,46966 46966 - Spectrin repeat 46966 - Spectrin repeat 46966 - Spectrin repeat	0.1454	INHERITED FROM: Achilles tendon contracture || Contractures involving the joints of the feet || Abnormality of the musculature of the lower limbs || Abnormality of the Achilles tendon
48726,48726,48726 48726 - Immunoglobulin 48726 - Immunoglobulin 48726 - Immunoglobulin	0.1701	INHERITED FROM: Abnormality of the middle phalanges of the toes || Rocker bottom foot || Short middle phalanx of toe || Abnormality of the tarsal bones
57184,57196,57184 57184 - Growth factor receptor domain 57196 - EGF/Laminin 57184 - Growth factor receptor domain	0.4121	INHERITED FROM: Abnormality of the knee
57184,57184,57196 57184 - Growth factor receptor domain 57184 - Growth factor receptor domain 57196 - EGF/Laminin	0.4121	INHERITED FROM: Aplasia/Hypoplasia involving bones of the feet
57196,57196,57184 57196 - EGF/Laminin 57196 - EGF/Laminin 57184 - Growth factor receptor domain	0.8512	INHERITED FROM: Absent toe