Intellectual disability, autosomal recessive 3

Summary

Intellectual disability, autosomal recessive 3 (MONDO:0012037) is a disease caused by CC2D1A (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: CC2D1A (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 70

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual disability, autosomal recessive 3
Mondo ID	MONDO:0012037
MeSH	C563929
OMIM	608443
DOID	DOID:0081179
UMLS	C1838023
MedGen	373870
GARD	0022539
Is cancer (heuristic)	no

Also known as: autosomal recessive non-syndromic intellectual disability caused by mutation in CC2D1A · CC2D1A autosomal recessive non-syndromic intellectual disability · intellectual disability, autosomal recessive 3 · intellectual disability, autosomal recessive type 3 · mental retardation, autosomal recessive 3 · mental retardation, autosomal recessive type 3 · MRT3

Data availability: 70 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › neurodevelopmental disorder › intellectual disability › non-syndromic intellectual disability › autosomal recessive non-syndromic intellectual disability › intellectual disability, autosomal recessive 3

Related subtypes (67): intellectual disability, autosomal recessive 1, intellectual disability, autosomal recessive 2, intellectual disability, autosomal recessive 12, intellectual disability, autosomal recessive 5, intellectual disability, autosomal recessive 6, intellectual disability, autosomal recessive 7, intellectual disability, autosomal recessive 9, intellectual disability, autosomal recessive 10, intellectual disability, autosomal recessive 11, intellectual disability, autosomal recessive 4, intellectual disability, autosomal recessive 13, intellectual disability, autosomal recessive 14, Rafiq syndrome, intellectual disability, autosomal recessive 16, intellectual disability, autosomal recessive 18, intellectual disability, autosomal recessive 31, intellectual disability, autosomal recessive 29, intellectual disability, autosomal recessive 27, intellectual disability, autosomal recessive 33, intellectual disability, autosomal recessive 30, intellectual disability, autosomal recessive 19, intellectual disability, autosomal recessive 23, intellectual disability, autosomal recessive 24, intellectual disability, autosomal recessive 25, intellectual disability, autosomal recessive 28, intellectual disability, autosomal recessive 34, intellectual disability, autosomal recessive 42, intellectual disability, autosomal recessive 43, intellectual disability, autosomal recessive 44, intellectual disability, autosomal recessive 45, intellectual disability, autosomal recessive 46, intellectual disability, autosomal recessive 47, Al-Raqad syndrome, intellectual disability, autosomal recessive 50, intellectual disability, autosomal recessive 51, intellectual disability, autosomal recessive 52, intellectual disability, autosomal recessive 54, intellectual disability, autosomal recessive 56, intellectual developmental disorder, autosomal recessive 74, intellectual disability, autosomal recessive 57, intellectual disability, autosomal recessive 58, intellectual disability, autosomal recessive 59, pontocerebellar hypoplasia type 1, intellectual disability, autosomal recessive 64, intellectual disability, autosomal recessive 65, intellectual developmental disorder, autosomal recessive 73, intellectual developmental disorder, autosomal recessive 75, with neuropsychiatric features and variant lissencephaly, intellectual disability, autosomal recessive 61, intellectual developmental disorder, autosomal recessive 76, intellectual developmental disorder, autosomal recessive 77, intellectual disability, autosomal recessive 66, intellectual developmental disorder, autosomal recessive 67, intellectual developmental disorder, autosomal recessive 68, intellectual developmental disorder, autosomal recessive 69, intellectual developmental disorder, autosomal recessive 70, intellectual developmental disorder, autosomal recessive 71, intellectual developmental disorder, autosomal recessive 72, glycosylphosphatidylinositol biosynthesis defect 16, intellectual disability, autosomal recessive 60, intellectual disability, autosomal recessive 63, adenosine kinase deficiency, intellectual developmental disorder, autosomal recessive 78, intellectual developmental disorder, autosomal recessive 79, intellectual developmental disorder, autosomal recessive 80, with variant lissencephaly, intellectual developmental disorder, autosomal recessive 81, intellectual developmental disorder, autosomal recessive 82, intellectual developmental disorder, autosomal recessive 83

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

70 retrieved; paginated sample, class counts are floors:

26 uncertain significance, 20 conflicting classifications of pathogenicity, 13 likely pathogenic, 3 benign/likely benign, 3 pathogenic, 3 pathogenic/likely pathogenic, 2 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1322031	NM_017721.5(CC2D1A):c.1764+1G>C	CC2D1A	Pathogenic	criteria provided, single submitter
228325	NM_017721.5(CC2D1A):c.748+1G>T	CC2D1A	Pathogenic	criteria provided, multiple submitters, no conflicts
2753777	NM_017721.5(CC2D1A):c.1061dup (p.Arg355fs)	CC2D1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2820289	NM_017721.5(CC2D1A):c.179_180insCA (p.Glu60fs)	CC2D1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
984700	NM_017721.5(CC2D1A):c.2693del (p.Gly898fs)	CC2D1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1354	NM_017721.5(CC2D1A):c.1223-294_1642-220del	LOC129391070	Pathogenic	no assertion criteria provided
1324018	NM_017721.5(CC2D1A):c.511_513+1del	CC2D1A	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1751762	NM_017721.5(CC2D1A):c.61-2A>G	CC2D1A	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2732136	NM_017721.5(CC2D1A):c.2454+1G>A	CC2D1A	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2865268	NM_017721.5(CC2D1A):c.2225+1G>A	CC2D1A	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2991173	NM_017721.5(CC2D1A):c.2710+1G>A	CC2D1A	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3064197	NM_017721.5(CC2D1A):c.2711-2A>G	CC2D1A	Likely pathogenic	criteria provided, single submitter
3376456	NM_017721.5(CC2D1A):c.959dup (p.Asp321fs)	CC2D1A	Likely pathogenic	criteria provided, single submitter
3583504	NM_017721.5(CC2D1A):c.1117_1121dup (p.Lys374fs)	CC2D1A	Likely pathogenic	criteria provided, single submitter
3583505	NM_017721.5(CC2D1A):c.1403C>G (p.Ser468Ter)	CC2D1A	Likely pathogenic	criteria provided, single submitter
3583506	NM_017721.5(CC2D1A):c.1468+1G>C	CC2D1A	Likely pathogenic	criteria provided, single submitter
3583507	NM_017721.5(CC2D1A):c.1528C>T (p.Arg510Ter)	CC2D1A	Likely pathogenic	criteria provided, single submitter
4081231	NM_017721.5(CC2D1A):c.197-1G>A	CC2D1A	Likely pathogenic	criteria provided, single submitter
982864	NM_017721.5(CC2D1A):c.1620_1623dup (p.Pro542fs)	CC2D1A	Likely pathogenic	criteria provided, single submitter
1030587	NM_017721.5(CC2D1A):c.2495C>G (p.Ala832Gly)	CC2D1A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
128614	NM_017721.5(CC2D1A):c.1192G>A (p.Val398Met)	CC2D1A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
128618	NM_017721.5(CC2D1A):c.1739C>T (p.Thr580Ile)	CC2D1A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1702973	NM_017721.5(CC2D1A):c.1276G>A (p.Val426Met)	CC2D1A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1794973	NM_017721.5(CC2D1A):c.2705G>A (p.Arg902Gln)	CC2D1A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
210590	NM_017721.5(CC2D1A):c.1234A>G (p.Ile412Val)	CC2D1A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
210593	NM_017721.5(CC2D1A):c.1424C>T (p.Ser475Leu)	CC2D1A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
210594	NM_017721.5(CC2D1A):c.1448C>A (p.Pro483His)	CC2D1A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
210598	NM_017721.5(CC2D1A):c.2048G>A (p.Arg683Gln)	CC2D1A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
210600	NM_017721.5(CC2D1A):c.2342G>C (p.Gly781Ala)	CC2D1A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
210604	NM_017721.5(CC2D1A):c.2764C>T (p.Arg922Cys)	CC2D1A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
CC2D1A	Definitive	Autosomal recessive	intellectual disability, autosomal recessive 3	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CC2D1A	Orphanet:88616	Autosomal recessive non-syndromic intellectual disability

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
CC2D1A	HGNC:30237	ENSG00000132024	Q6P1N0	Coiled-coil and C2 domain-containing protein 1A	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CC2D1A	Coiled-coil and C2 domain-containing protein 1A	Transcription factor that binds specifically to the DRE (dual repressor element) and represses HTR1A gene transcription in neuronal cells.

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)
CC2D1A	Other/Unknown	no		C2_dom, CC2D1A/B_DM14, C2_domain_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
cerebellar hemisphere	1
mucosa of transverse colon	1
right hemisphere of cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CC2D1A	134	ubiquitous	marker	right hemisphere of cerebellum, mucosa of transverse colon, cerebellar hemisphere

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CC2D1A	1,127

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CC2D1A	Q6P1N0	74.71

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
apical dendrite arborization	1	16852.0×	3e-04	CC2D1A
negative regulation of snRNA transcription by RNA polymerase II	1	16852.0×	3e-04	CC2D1A
regulation of respiratory gaseous exchange by nervous system process	1	1296.3×	0.003	CC2D1A
endosome organization	1	374.5×	0.005	CC2D1A
regulation of postsynapse assembly	1	343.9×	0.005	CC2D1A
long-term synaptic potentiation	1	280.9×	0.005	CC2D1A
social behavior	1	271.8×	0.005	CC2D1A
learning or memory	1	240.7×	0.005	CC2D1A
positive regulation of canonical NF-kappaB signal transduction	1	72.6×	0.015	CC2D1A
regulation of transcription by RNA polymerase II	1	11.7×	0.086	CC2D1A

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
CC2D1A	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	CC2D1A

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)
CC2D1A	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.