Hereditary anorectal anomalies

Summary

Hereditary anorectal anomalies (MONDO:0007136) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hereditary anorectal anomalies
Mondo ID	MONDO:0007136
MeSH	C567938
OMIM	107100
UMLS	C3495676
MedGen	501217
GARD	0024524
Is cancer (heuristic)	no

Also known as: genetic anorectal anomalies

Data availability: 1 ClinVar variant.

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › disorder of development or morphogenesis › anorectal malformation › hereditary anorectal anomalies

Related subtypes (4): rectal duplication, non-syndromic anorectal malformation with rectourethral fistula, bulbar type, non-syndromic anorectal malformation with rectourethral fistula, prostatic type, isolated anal canal duplication

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

1 retrieved; paginated sample, class counts are floors:

1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
4279065	NM_000285.4(PEPD):c.1164dup (p.Ile389fs)	PEPD	Likely pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

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

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PEPD	Orphanet:742	Prolidase deficiency

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
PEPD	HGNC:8840	ENSG00000124299	P12955	Xaa-Pro dipeptidase	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PEPD	Xaa-Pro dipeptidase	Dipeptidase that catalyzes the hydrolysis of dipeptides with a prolyl (Xaa-Pro) or hydroxyprolyl residue in the C-terminal position.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Protease	1	36.6×	0.027

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PEPD	Protease	yes	3.4.13.9	Pept_M24, Peptidase_M24B_aminopep-P_CS, Aminopep_P_N

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
adult mammalian kidney	1
ileal mucosa	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PEPD	276	ubiquitous	marker	ileal mucosa, adult mammalian kidney, right lobe of liver

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PEPD	2,471

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PEPD	P12955	21

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
amino acid metabolic process	1	802.5×	0.003	PEPD
negative regulation of programmed cell death	1	732.7×	0.003	PEPD
collagen catabolic process	1	391.9×	0.003	PEPD
proteolysis	1	34.2×	0.029	PEPD

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
PEPD	CAPTOPRIL

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PEPD	4	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CAPTOPRIL	4	PEPD
DAUNORUBICIN	4	PEPD
DOXORUBICIN	4	PEPD
GENTAMICIN	4	PEPD

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
PEPD	31	Binding:31

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PEPD	3.4.13.9	Xaa-Pro dipeptidase

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

4 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.

Compound	Max phase	Cohort target (bioactivity)
CAPTOPRIL	4	PEPD
DAUNORUBICIN	4	PEPD
DOXORUBICIN	4	PEPD
GENTAMICIN	4	PEPD

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	PEPD
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	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.