Postaxial polydactyly of fingers

Summary

Postaxial polydactyly of fingers (MONDO:0017426) is a disease with 6 cohort genes.

At a glance

• Cohort genes: 6
• ClinVar variants: 7

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	postaxial polydactyly of fingers
Mondo ID	MONDO:0017426
Orphanet	294942
ICD-11	1146378807
SNOMED CT	205131007
UMLS	C0431904
MedGen	609221
GARD	0012460
Is cancer (heuristic)	no

Also known as: postaxial polydactyly of hand

Data availability: 7 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › polydactyly › non-syndromic polydactyly › postaxial polydactyly of fingers

Related subtypes (9): polysyndactyly 4, synpolydactyly type 1, synpolydactyly type 2, preaxial polydactyly of fingers, central polydactyly of fingers, Preaxial polydactyly of toes, megalencephaly-polymicrogyria-postaxial polydactyly-hydrocephalus syndrome, postaxial polydactyly, mirror-image polydactyly

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

7 retrieved; paginated sample, class counts are floors:

3 pathogenic, 2 conflicting classifications of pathogenicity, 1 pathogenic/likely pathogenic, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
626905	NM_001195305.3(BBIP1):c.109C>T (p.Gln37Ter)	BBIP1	Pathogenic	no assertion criteria provided
225010	NM_024685.4(BBS10):c.145C>T (p.Arg49Trp)	BBS10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
9641	NC_012920.1(MT-ATP6):m.8993T>G	MT-ATP6	Pathogenic	reviewed by expert panel
30544	NM_004278.4(PIGL):c.500T>C (p.Leu167Pro)	PIGL	Pathogenic	criteria provided, multiple submitters, no conflicts
627565	NM_000168.6(GLI3):c.1622C>T (p.Thr541Met)	GLI3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
374124	NM_198525.3(KIF7):c.434A>C (p.Tyr145Ser)	KIF7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
374175	NM_004278.4(PIGL):c.176C>A (p.Pro59His)	PIGL	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 22 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BBS10	Orphanet:110	Bardet-Biedl syndrome
BBIP1	Orphanet:110	Bardet-Biedl syndrome
KIF7	Orphanet:166024	Multiple epiphyseal dysplasia-macrocephaly-facial dysmorphism syndrome
KIF7	Orphanet:2189	Hydrolethalus
KIF7	Orphanet:2754	Orofaciodigital syndrome type 6
KIF7	Orphanet:36	Acrocallosal syndrome
GLI3	Orphanet:36	Acrocallosal syndrome
GLI3	Orphanet:380	Greig cephalopolysyndactyly syndrome
GLI3	Orphanet:672	Pallister-Hall syndrome
GLI3	Orphanet:93322	Isolated tibial hemimelia
GLI3	Orphanet:93334	Postaxial polydactyly type A
GLI3	Orphanet:93335	Postaxial polydactyly type B
GLI3	Orphanet:93338	Polysyndactyly
MT-ATP6	Orphanet:104	Leber hereditary optic neuropathy
MT-ATP6	Orphanet:225154	Familial infantile bilateral striatal necrosis
MT-ATP6	Orphanet:254913	Isolated ATP synthase deficiency
MT-ATP6	Orphanet:255210	Mitochondrial DNA-associated Leigh syndrome
MT-ATP6	Orphanet:320360	MT-ATP6-related mitochondrial spastic paraplegia
MT-ATP6	Orphanet:397750	Periodic paralysis with later-onset distal motor neuropathy
MT-ATP6	Orphanet:644	NARP syndrome
PIGL	Orphanet:247262	Hyperphosphatasia-intellectual disability syndrome
PIGL	Orphanet:3474	CHIME syndrome

Cohort genes → proteins

6 cohort genes, 6 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	6

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
BBS10	HGNC:26291	ENSG00000179941	Q8TAM1	BBSome complex assembly protein BBS10	clinvar
BBIP1	HGNC:28093	ENSG00000214413	A8MTZ0	BBSome-interacting protein 1	clinvar
KIF7	HGNC:30497	ENSG00000166813	Q2M1P5	Kinesin-like protein KIF7	clinvar
GLI3	HGNC:4319	ENSG00000106571	P10071	Transcriptional activator GLI3	clinvar
MT-ATP6	HGNC:7414	ENSG00000198899	P00846	ATP synthase F(0) complex subunit a	clinvar
PIGL	HGNC:8966	ENSG00000108474	Q9Y2B2	N-acetylglucosaminyl-phosphatidylinositol de-N-acetylase	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BBS10	BBSome complex assembly protein BBS10	Probable molecular chaperone that assists the folding of proteins upon ATP hydrolysis.
BBIP1	BBSome-interacting protein 1	The BBSome complex is thought to function as a coat complex required for sorting of specific membrane proteins to the primary cilia.
KIF7	Kinesin-like protein KIF7	Essential for hedgehog signaling regulation: acts both as a negative and positive regulator of sonic hedgehog (Shh) and Indian hedgehog (Ihh) pathways, acting downstream of SMO, through both SUFU-dependent and -independent mechanisms.
GLI3	Transcriptional activator GLI3	Has a dual function as a transcriptional activator and a repressor of the sonic hedgehog (Shh) pathway, and plays a role in limb development.
MT-ATP6	ATP synthase F(0) complex subunit a	Subunit a, of the mitochondrial membrane ATP synthase complex (F(1)F(0) ATP synthase or Complex V) that produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of th…
PIGL	N-acetylglucosaminyl-phosphatidylinositol de-N-acetylase	Catalyzes the second step of glycosylphosphatidylinositol (GPI) biosynthesis, which is the de-N-acetylation of N-acetylglucosaminyl-phosphatidylinositol.

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 4 · Druggable fraction: 0.17

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Enzyme (other)	1	2.0×	0.539
Transcription factor	1	1.4×	0.539
Other/Unknown	4	1.2×	0.539

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BBS10	Other/Unknown	no		Cpn60/GroEL/TCP-1, GroEL-like_apical_dom_sf, TCP-1-like_intermed_sf
BBIP1	Other/Unknown	no		BBIP10
KIF7	Other/Unknown	no		Kinesin_motor_dom, Kinesin_motor_CS, P-loop_NTPase
GLI3	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, GLI-like
MT-ATP6	Other/Unknown	no		ATP_synth_F0_asu, ATP_synth_F0_asu_AS, F0_ATP_A_sf
PIGL	Enzyme (other)	yes	3.5.1.89	GlcNAc_PI_deacetylase-related, LmbE-like_dom_sf

Expression context

Cohort genes with no expression data: 0.

4 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	6
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ventricular zone	2
mucosa of stomach	2
calcaneal tendon	1
endothelial cell	1
buccal mucosa cell	1
epithelium of nasopharynx	1
sperm	1
cardiac muscle of right atrium	1
kidney epithelium	1
left ventricle myocardium	1
olfactory bulb	1
tendon of biceps brachii	1
descending thoracic aorta	1
left uterine tube	1
right uterine tube	1
sural nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BBS10	253	ubiquitous	yes	calcaneal tendon, endothelial cell, ventricular zone
BBIP1	288	ubiquitous	marker	epithelium of nasopharynx, buccal mucosa cell, sperm
KIF7	165	ubiquitous	yes	kidney epithelium, cardiac muscle of right atrium, left ventricle myocardium
GLI3	263	ubiquitous	marker	ventricular zone, olfactory bulb, tendon of biceps brachii
MT-ATP6	134	ubiquitous	marker	mucosa of stomach, left uterine tube, descending thoracic aorta
PIGL	236	ubiquitous	marker	mucosa of stomach, right uterine tube, sural nerve

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BBS10	3,224
MT-ATP6	2,869
GLI3	2,825
KIF7	1,655
PIGL	995
BBIP1	29

Intra-cohort edges

A	B	Sources
GLI3	KIF7	string_interaction

Structural data

PDB: 4 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MT-ATP6	P00846	10
KIF7	Q2M1P5	5
BBIP1	A8MTZ0	1
GLI3	P10071	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PIGL	Q9Y2B2	91.66
BBS10	Q8TAM1	71.26

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 20. Enrichment computed across 6 evidence-associated genes (6 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
BBSome-mediated cargo-targeting to cilium	2	165.5×	7e-04	BBS10, BBIP1
Organelle biogenesis and maintenance	3	33.0×	7e-04	BBS10, BBIP1, MT-ATP6
Cargo trafficking to the periciliary membrane	2	82.8×	0.002	BBS10, BBIP1
Hedgehog ‘off’ state	2	59.5×	0.002	KIF7, GLI3
Hedgehog ‘on’ state	2	52.9×	0.002	KIF7, GLI3
Cilium Assembly	2	36.2×	0.004	BBS10, BBIP1
GLI proteins bind promoters of Hh responsive genes to promote transcription	1	271.9×	0.010	GLI3
Synthesis of glycosylphosphatidylinositol (GPI)	1	105.7×	0.023	PIGL
Formation of ATP by chemiosmotic coupling	1	95.2×	0.023	MT-ATP6
RUNX2 regulates osteoblast differentiation	1	76.1×	0.026	GLI3
Cristae formation	1	57.7×	0.031	MT-ATP6
GLI3 is processed to GLI3R by the proteasome	1	37.3×	0.044	GLI3
Signaling by Hedgehog	1	30.7×	0.049	KIF7
Mitochondrial biogenesis	1	28.0×	0.050	MT-ATP6
Mitochondrial protein degradation	1	19.0×	0.067	MT-ATP6
Mitochondrial translation termination	1	18.3×	0.067	MT-ATP6
Aerobic respiration and respiratory electron transport	1	14.8×	0.078	MT-ATP6
Metabolism of proteins	1	2.1×	0.439	MT-ATP6
Metabolism	1	1.9×	0.439	MT-ATP6
Signal Transduction	1	1.7×	0.463	KIF7

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
lateral ganglionic eminence cell proliferation	1	2808.7×	0.005	GLI3
lambdoid suture morphogenesis	1	2808.7×	0.005	GLI3
sagittal suture morphogenesis	1	2808.7×	0.005	GLI3
mammary gland specification	1	2808.7×	0.005	GLI3
anterior semicircular canal development	1	2808.7×	0.005	GLI3
lateral semicircular canal development	1	2808.7×	0.005	GLI3
negative regulation of smoothened signaling pathway	2	151.8×	0.005	KIF7, GLI3
smoothened signaling pathway involved in ventral spinal cord interneuron specification	1	1404.3×	0.007	GLI3
smoothened signaling pathway involved in spinal cord motor neuron cell fate specification	1	1404.3×	0.007	GLI3
larynx morphogenesis	1	1404.3×	0.007	GLI3
retinal cone cell differentiation	1	936.2×	0.007	BBS10
nose morphogenesis	1	936.2×	0.007	GLI3
negative regulation of alpha-beta T cell differentiation	1	936.2×	0.007	GLI3
frontal suture morphogenesis	1	936.2×	0.007	GLI3
cell differentiation involved in kidney development	1	936.2×	0.007	GLI3
hindgut morphogenesis	1	702.2×	0.008	GLI3
smoothened signaling pathway involved in dorsal/ventral neural tube patterning	1	702.2×	0.008	GLI3
cone retinal bipolar cell differentiation	1	702.2×	0.008	BBS10
optic nerve morphogenesis	1	561.7×	0.008	GLI3
receptor localization to non-motile cilium	1	561.7×	0.008	BBIP1
regulation of bone development	1	561.7×	0.008	GLI3
forebrain radial glial cell differentiation	1	468.1×	0.010	GLI3
forebrain dorsal/ventral pattern formation	1	351.1×	0.012	GLI3
tongue development	1	351.1×	0.012	GLI3
alpha-beta T cell differentiation	1	312.1×	0.012	GLI3
embryonic neurocranium morphogenesis	1	312.1×	0.012	GLI3
retinal rod cell differentiation	1	312.1×	0.012	BBS10
positive regulation of alpha-beta T cell differentiation	1	280.9×	0.013	GLI3
negative thymic T cell selection	1	234.1×	0.014	GLI3
artery development	1	234.1×	0.014	GLI3

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 6

Druggability breadth: 2 of 6 evidence-associated genes (33%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
BBS10	0	0
BBIP1	0	0
KIF7	0	0
GLI3	0	0
MT-ATP6	0	0
PIGL	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
KIF7	5	Binding:5
MT-ATP6	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PIGL	3.5.1.89	N-acetylglucosaminylphosphatidylinositol deacetylase

Pharmacogenomics

Cohort genes with a PharmGKB record: 6; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	PIGL
E	Difficult family or no structure, no drug	5	BBS10, BBIP1, KIF7, GLI3, MT-ATP6

Undrugged target profiles

6 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
BBS10	0	—
BBIP1	0	—
KIF7	5	—
GLI3	0	—
MT-ATP6	1	—
PIGL	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.