Anencephaly 1

Summary

Anencephaly 1 (MONDO:0008791) is a disease with 1 cohort gene and 2 clinical trials.

At a glance

• Prevalence: 1-9 / 1 000 000 (Europe) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 2
• Phenotypes (HPO): 2
• Clinical trials: 2

Clinical features

Epidemiology

Prevalence records

9 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Prevalence at birth	1-9 / 100 000	5.1	Worldwide	Validated
Point prevalence	1-9 / 1 000 000		Europe	Validated
Prevalence at birth	1-5 / 10 000	4.22	Europe	Validated
Prevalence at birth	1-5 / 10 000	20.6	United States	Validated
Prevalence at birth	>1 / 1000	210	India	Validated
Prevalence at birth	>1 / 1000	120	Iran, Islamic Republic of	Validated
Prevalence at birth	1-5 / 10 000	58	Singapore	Validated
Prevalence at birth	>1 / 1000	1.4	Africa	Validated
Prevalence at birth	6-9 / 10 000	8.6	Australia	Validated

Signs & symptoms

Clinical features (HPO)

2 HPO clinical features (Orphanet curated; top 2 by frequency):

HPO ID	Term	Frequency
HP:0002323	Anencephaly	Very frequent (80-99%)
HP:0008207	Primary adrenal insufficiency	Very frequent (80-99%)

Identifiers

Disease identifiers

Field	Value
Canonical name	anencephaly 1
Mondo ID	MONDO:0008791
OMIM	206500
Orphanet	1048
SNOMED CT	89369001
UMLS	C5561928
MedGen	1794138
GARD	0005808
Is cancer (heuristic)	no

Also known as: absence of a large part of the brain and the skull · anencephaly · anencephaly 1 · ANPH · isolated anencephaly/exencephaly

Data availability: 2 ClinVar variants · 1 GenCC gene-disease record · 3 cell lines.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › congenital nervous system disorder › anencephaly › anencephaly 1

Related subtypes (3): hydranencephaly, anencephaly 2, isolated anencephaly

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

2 retrieved; paginated sample, class counts are floors:

2 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1342267	NM_001300759.2(TRIM36):c.1996G>A (p.Asp666Asn)	TRIM36	Benign	criteria provided, single submitter
1342268	NM_001300759.2(TRIM36):c.1797-35T>G	TRIM36	Benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 1 · Orphanet: 0 · 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
TRIM36	Limited	Unknown	anencephaly 1

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
TRIM36	HGNC:16280	ENSG00000152503	Q9NQ86	E3 ubiquitin-protein ligase TRIM36	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TRIM36	E3 ubiquitin-protein ligase TRIM36	E3 ubiquitin-protein ligase which mediates ubiquitination and subsequent proteasomal degradation of target proteins.

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)
TRIM36	Transcription factor	no		Znf_B-box, Znf_RING, B30.2/SPRY

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
secondary oocyte	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TRIM36	223	ubiquitous	marker	sperm, secondary oocyte, left testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TRIM36	1,248

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TRIM36	Q9NQ86	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
Antigen processing: Ubiquitination & Proteasome degradation	1	37.2×	0.027	TRIM36

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
spindle organization	1	991.3×	0.003	TRIM36
acrosome reaction	1	887.0×	0.003	TRIM36
regulation of microtubule cytoskeleton organization	1	543.6×	0.003	TRIM36
mitotic cytokinesis	1	259.3×	0.005	TRIM36
regulation of cell cycle	1	74.6×	0.013	TRIM36

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
TRIM36	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	TRIM36

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)
TRIM36	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 2.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00031122	Not specified	UNKNOWN	Study of Genetic Risk Factors for Spina Bifida and Anencephaly
NCT00636233	Not specified	COMPLETED	Genetics of Spina Bifida and Anencephaly