Intellectual disability, autosomal recessive 56

Summary

Intellectual disability, autosomal recessive 56 (MONDO:0014930) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 10

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual disability, autosomal recessive 56
Mondo ID	MONDO:0014930
OMIM	617125
DOID	DOID:0081217
UMLS	C4310703
MedGen	934670
GARD	0022574
Is cancer (heuristic)	no

Also known as: autosomal recessive non-syndromic intellectual disability caused by mutation in ZC3H14 · intellectual developmental disorder, autosomal recessive 56 · intellectual disability, autosomal recessive 56 · intellectual disability, autosomal recessive type 56 · mental retardation, autosomal recessive 56 · mental retardation, autosomal recessive type 56 · MRT56 · ZC3H14 autosomal recessive non-syndromic intellectual disability

Data availability: 10 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 56

Related subtypes (67): intellectual disability, autosomal recessive 1, intellectual disability, autosomal recessive 2, intellectual disability, autosomal recessive 3, 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 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

10 retrieved; paginated sample, class counts are floors:

4 uncertain significance, 2 conflicting classifications of pathogenicity, 1 benign/likely benign, 1 benign, 1 no classifications from unflagged records, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
254279	NM_024824.5(ZC3H14):c.2204+17_2204+41del	ZC3H14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
728973	NM_024824.5(ZC3H14):c.853A>T (p.Ser285Cys)	ZC3H14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1029539	NM_024824.5(ZC3H14):c.1280-1856A>G	ZC3H14	Uncertain significance	criteria provided, single submitter
1030880	NM_024824.5(ZC3H14):c.1232C>T (p.Pro411Leu)	ZC3H14	Uncertain significance	criteria provided, single submitter
1031409	NM_024824.5(ZC3H14):c.1133A>G (p.Lys378Arg)	ZC3H14	Uncertain significance	criteria provided, multiple submitters, no conflicts
1031410	NM_024824.5(ZC3H14):c.311G>A (p.Arg104Gln)	ZC3H14	Uncertain significance	criteria provided, multiple submitters, no conflicts
254278	NM_024824.5(ZC3H14):c.460C>T (p.Arg154Ter)	ZC3H14	no classifications from unflagged records	no classifications from unflagged records
130767	NM_024824.5(ZC3H14):c.432-3T>C	ZC3H14	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
1684249	NM_024824.5(ZC3H14):c.1354+15A>G	ZC3H14	Benign	criteria provided, multiple submitters, no conflicts
915328	NM_024824.5(ZC3H14):c.1424C>T (p.Ser475Phe)	ZC3H14	Likely 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
ZC3H14	Moderate	Autosomal recessive	intellectual disability, autosomal recessive 56	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ZC3H14	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
ZC3H14	HGNC:20509	ENSG00000100722	Q6PJT7	Zinc finger CCCH domain-containing protein 14	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ZC3H14	Zinc finger CCCH domain-containing protein 14	RNA-binding protein involved in the biogenesis of circular RNAs (circRNAs), which are produced by back-splicing circularization of pre-mRNAs.

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)
ZC3H14	Transcription factor	no		Znf_CCCH, Nab2/ZC3H14

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
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ZC3H14	298	ubiquitous	marker	left testis, right testis, sperm

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ZC3H14	2,613

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ZC3H14	Q6PJT7	56.87

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
spliceosome-depend formation of circular RNA	1	3370.4×	0.001	ZC3H14
regulation of mRNA stability	1	421.3×	0.005	ZC3H14
mRNA stabilization	1	366.4×	0.005	ZC3H14
spermatogenesis	1	35.2×	0.034	ZC3H14
cell differentiation	1	29.1×	0.034	ZC3H14

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
ZC3H14	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	ZC3H14

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)
ZC3H14	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.