familial clubfoot due to PITX1 point mutation

Summary

familial clubfoot due to PITX1 point mutation (MONDO:0017383) is a disease caused by PITX1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: PITX1 (GenCC Strong)
• Cohort genes: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	familial clubfoot due to PITX1 point mutation
Mondo ID	MONDO:0017383
Orphanet	293150
UMLS	C5679943
MedGen	1814442
GARD	0017337
Is cancer (heuristic)	no

Also known as: hereditary clubfoot due to PITX1 point mutation

Data availability: 1 GenCC gene-disease record · 1 cell line.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › familial clubfoot with or without associated lower limb anomalies › clubfoot › familial clubfoot due to PITX1 point mutation

Related subtypes (1): familial clubfoot due to 5q31 microdeletion

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 4 · 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
PITX1	Strong	Autosomal dominant	familial clubfoot due to PITX1 point mutation	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PITX1	Orphanet:1275	Brachydactyly-elbow wrist dysplasia syndrome
PITX1	Orphanet:293144	Familial clubfoot due to 5q31 microdeletion
PITX1	Orphanet:293150	Familial clubfoot due to PITX1 point mutation
PITX1	Orphanet:498494	Mirror-image polydactyly

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
PITX1	HGNC:9004	ENSG00000069011	P78337	Pituitary homeobox 1	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PITX1	Pituitary homeobox 1	Sequence-specific transcription factor that binds gene promoters and activates their transcription.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PITX1	Transcription factor	no		HD, OAR_dom, Homeodomain-like_sf

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
esophagus mucosa	1
lower esophagus mucosa	1
pharyngeal mucosa	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PITX1	180	broad	marker	lower esophagus mucosa, esophagus mucosa, pharyngeal mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PITX1	1,884

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PITX1	P78337	62.81

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
branchiomeric skeletal muscle development	1	5617.3×	0.001	PITX1
myoblast fate commitment	1	3370.4×	0.001	PITX1
pituitary gland development	1	648.1×	0.004	PITX1
embryonic hindlimb morphogenesis	1	581.1×	0.004	PITX1
cartilage development	1	251.5×	0.007	PITX1
anatomical structure morphogenesis	1	139.3×	0.010	PITX1
skeletal system development	1	125.8×	0.010	PITX1
negative regulation of DNA-templated transcription	1	31.6×	0.036	PITX1
regulation of transcription by RNA polymerase II	1	11.7×	0.086	PITX1

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
PITX1	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	PITX1

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)
PITX1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.