Polydactyly, postaxial, type a7

Summary

Polydactyly, postaxial, type a7 (MONDO:0060550) is a disease caused by IQCE (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: IQCE (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 31

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	polydactyly, postaxial, type a7
Mondo ID	MONDO:0060550
OMIM	617642
UMLS	C4539976
MedGen	1627079
GARD	0025999
Is cancer (heuristic)	no

Also known as: PAPA7

Data availability: 31 ClinVar variants · 3 GenCC gene-disease records.

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 › postaxial polydactyly type A › polydactyly, postaxial, type a7

Related subtypes (9): polydactyly, postaxial, type A1, polydactyly, postaxial, type A5, polydactyly, postaxial, type A2, polydactyly, postaxial, type A3, polydactyly, postaxial, type A4, polydactyly, postaxial, type A6, postaxial polydactyly type A, unilateral, postaxial polydactyly type A, bilateral, polydactyly, postaxial, type A8

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

31 retrieved; paginated sample, class counts are floors:

17 benign, 5 pathogenic, 4 likely pathogenic, 3 uncertain significance, 2 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
3377144	NM_152558.5(IQCE):c.1540del (p.Cys514fs)	IQCE	Pathogenic	criteria provided, single submitter
3377151	NM_152558.5(IQCE):c.1493G>A (p.Trp498Ter)	IQCE	Pathogenic	criteria provided, single submitter
437834	NM_152558.5(IQCE):c.395-1G>A	IQCE	Pathogenic	no assertion criteria provided
4530591	NM_152558.5(IQCE):c.765C>G (p.Tyr255Ter)	IQCE	Pathogenic	criteria provided, single submitter
638150	NM_152558.5(IQCE):c.1350_1353del	IQCE	Pathogenic	criteria provided, multiple submitters, no conflicts
1030264	NM_152558.5(IQCE):c.3G>A (p.Met1Ile)	IQCE	Likely pathogenic	criteria provided, single submitter
2506557	GRCh37/hg19 7p22.3(chr7:2606751-2641098)	IQCE	Likely pathogenic	criteria provided, single submitter
3065859	NM_152558.5(IQCE):c.1616dup (p.Ala540fs)	IQCE	Likely pathogenic	criteria provided, single submitter
3776155	NM_152558.5(IQCE):c.323del (p.Gly108fs)	LOC126859928	Likely pathogenic	criteria provided, single submitter
638149	NM_152558.5(IQCE):c.895_904del (p.Val301fs)	IQCE	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
871385	NM_152558.5(IQCE):c.572_579+1del	IQCE	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3779771	NM_152558.5(IQCE):c.1969+117dup	IQCE	Uncertain significance	criteria provided, single submitter
3779772	NM_152558.5(IQCE):c.825-2A>G	IQCE	Uncertain significance	criteria provided, single submitter
977081	NM_152558.5(IQCE):c.1843C>T (p.His615Tyr)	IQCE	Uncertain significance	criteria provided, single submitter
1300036	NM_152558.5(IQCE):c.1996T>G (p.Leu666Val)	IQCE	Benign	criteria provided, single submitter
1300037	NM_152558.5(IQCE):c.2069C>T (p.Thr690Met)	IQCE	Benign	criteria provided, single submitter
1300038	NM_152558.5(IQCE):c.*23C>T	IQCE	Benign	criteria provided, single submitter
1300115	NM_152558.5(IQCE):c.312T>C (p.Thr104=)	IQCE	Benign	criteria provided, single submitter
1300116	NM_152558.5(IQCE):c.395-10G>C	IQCE	Benign	criteria provided, single submitter
1300117	NM_152558.5(IQCE):c.405T>C (p.Pro135=)	IQCE	Benign	criteria provided, single submitter
1300118	NM_152558.5(IQCE):c.465+11G>A	IQCE	Benign	criteria provided, single submitter
1300119	NM_152558.5(IQCE):c.774+8G>A	IQCE	Benign	criteria provided, single submitter
1300120	NM_152558.5(IQCE):c.825-4C>T	IQCE	Benign	criteria provided, single submitter
1300121	NM_152558.5(IQCE):c.1609-5dup	IQCE	Benign	criteria provided, single submitter
1300122	NM_152558.5(IQCE):c.1637C>T (p.Ala546Val)	IQCE	Benign	criteria provided, single submitter
1300123	NM_152558.5(IQCE):c.1725G>T (p.Val575=)	IQCE	Benign	criteria provided, single submitter
1300124	NM_152558.5(IQCE):c.1760G>A (p.Arg587His)	IQCE	Benign	criteria provided, single submitter
1300125	NM_152558.5(IQCE):c.1786A>G (p.Thr596Ala)	IQCE	Benign	criteria provided, single submitter
1300126	NM_152558.5(IQCE):c.1904G>A (p.Arg635Lys)	IQCE	Benign	criteria provided, single submitter
1300127	NM_152558.5(IQCE):c.1970-5T>C	IQCE	Benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
IQCE	Strong	Autosomal recessive	polydactyly, postaxial, type a7	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
IQCE	Orphanet:93334	Postaxial polydactyly type A

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
IQCE	HGNC:29171	ENSG00000106012	Q6IPM2	IQ domain-containing protein E	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
IQCE	IQ domain-containing protein E	Component of the EvC complex that positively regulates ciliary Hedgehog (Hh) signaling.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
IQCE	Other/Unknown	no		IQ_motif_EF-hand-BS, CellDiv_DevSignal_Domain

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
left testis	1
right testis	1
sural nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
IQCE	231	ubiquitous	marker	left testis, right testis, sural nerve

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
IQCE	1,124

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
IQCE	Q6IPM2	69.36

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. Enrichment computed across 1 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Activation of SMO	1	634.4×	0.006	IQCE
Signaling by Hedgehog	1	184.2×	0.008	IQCE
Hedgehog ‘on’ state	1	158.6×	0.008	IQCE
Signal Transduction	1	10.2×	0.098	IQCE

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
limb morphogenesis	1	1053.2×	9e-04	IQCE

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
IQCE	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; 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	0
E	Difficult family or no structure, no drug	1	IQCE

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
IQCE	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.