Intellectual disability, autosomal recessive 54

Summary

Intellectual disability, autosomal recessive 54 (MONDO:0014876) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 14

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual disability, autosomal recessive 54
Mondo ID	MONDO:0014876
OMIM	617028
DOID	DOID:0081216
UMLS	C4310755
MedGen	934722
GARD	0022573
Is cancer (heuristic)	no

Also known as: autosomal recessive non-syndromic intellectual disability caused by mutation in TNIK · intellectual developmental disorder 54 · intellectual disability, autosomal recessive 54 · intellectual disability, autosomal recessive type 54 · mental retardation, autosomal recessive 54 · mental retardation, autosomal recessive type 54 · MRT54 · TNIK autosomal recessive non-syndromic intellectual disability

Data availability: 14 ClinVar variants · 4 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 54

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 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

14 retrieved; paginated sample, class counts are floors:

7 benign, 5 uncertain significance, 1 pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
243022	NM_015028.4(TNIK):c.538C>T (p.Arg180Ter)	TNIK	Pathogenic	criteria provided, single submitter
1029340	NM_015028.4(TNIK):c.2869A>G (p.Met957Val)	TNIK	Uncertain significance	criteria provided, single submitter
1031854	NM_015028.4(TNIK):c.2724G>T (p.Thr908=)	TNIK	Uncertain significance	criteria provided, single submitter
1031855	NM_015028.4(TNIK):c.2729G>A (p.Gly910Glu)	TNIK	Uncertain significance	criteria provided, multiple submitters, no conflicts
1341778	NM_015028.4(TNIK):c.2737A>C (p.Lys913Gln)	TNIK	Uncertain significance	criteria provided, multiple submitters, no conflicts
2690243	NM_015028.4(TNIK):c.1633C>T (p.Arg545Trp)	TNIK	Uncertain significance	criteria provided, multiple submitters, no conflicts
1098861	NM_015028.4(TNIK):c.2995G>A (p.Ala999Thr)	TNIK	Benign	criteria provided, multiple submitters, no conflicts
1098862	NM_015028.4(TNIK):c.2682C>T (p.Ser894=)	TNIK	Benign	criteria provided, multiple submitters, no conflicts
1229404	NM_015028.4(TNIK):c.1419+19A>G	TNIK	Benign	criteria provided, multiple submitters, no conflicts
1342233	NM_015028.4(TNIK):c.2331G>C (p.Ala777=)	TNIK	Benign	criteria provided, multiple submitters, no conflicts
1342234	NM_015028.4(TNIK):c.2316C>T (p.Leu772=)	TNIK	Benign	criteria provided, multiple submitters, no conflicts
1342235	NM_015028.4(TNIK):c.744C>T (p.Asn248=)	TNIK	Benign	criteria provided, multiple submitters, no conflicts
1342236	NM_015028.4(TNIK):c.63C>T (p.Pro21=)	TNIK	Benign	criteria provided, multiple submitters, no conflicts
783409	NM_015028.4(TNIK):c.3012C>T (p.Ser1004=)	TNIK	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

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
TNIK	Moderate	Autosomal recessive	intellectual disability, autosomal recessive 54	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TNIK	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
TNIK	HGNC:30765	ENSG00000154310	Q9UKE5	TRAF2 and NCK-interacting protein kinase	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TNIK	TRAF2 and NCK-interacting protein kinase	Serine/threonine kinase that acts as an essential activator of the Wnt signaling pathway.

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
Kinase	1	27.7×	0.036

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TNIK	Kinase	yes		Prot_kinase_dom, CNH_dom, Ser/Thr_kinase_AS

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
caudate nucleus	1
cortical plate	1
oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TNIK	268	ubiquitous	marker	cortical plate, oocyte, caudate nucleus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TNIK	1,688

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TNIK	Q9UKE5	11

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
Oxidative Stress Induced Senescence	1	90.6×	0.011	TNIK

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
positive regulation of microvillus assembly	1	3370.4×	0.004	TNIK
regulation of dendrite morphogenesis	1	732.7×	0.008	TNIK
regulation of MAPK cascade	1	455.5×	0.009	TNIK
neuron projection morphogenesis	1	276.3×	0.011	TNIK
positive regulation of JNK cascade	1	163.6×	0.011	TNIK
MAPK cascade	1	153.2×	0.011	TNIK
protein autophosphorylation	1	145.3×	0.011	TNIK
cytoskeleton organization	1	132.7×	0.011	TNIK
Wnt signaling pathway	1	99.7×	0.013	TNIK
actin cytoskeleton organization	1	79.1×	0.015	TNIK
protein phosphorylation	1	68.0×	0.016	TNIK
intracellular signal transduction	1	38.1×	0.026	TNIK

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
TNIK	PONATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TNIK	46	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PONATINIB	4	TNIK
LENVATINIB	4	TNIK
AXITINIB	4	TNIK
SORAFENIB	4	TNIK
NERATINIB	4	TNIK
PACRITINIB	4	TNIK
VANDETANIB	4	TNIK
BOSUTINIB	4	TNIK
PAZOPANIB	4	TNIK
NINTEDANIB	4	TNIK
SUNITINIB	4	TNIK
DASATINIB	4	TNIK
ERLOTINIB	4	TNIK
QUIZARTINIB	4	TNIK
MIDOSTAURIN	4	TNIK
GEFITINIB	4	TNIK
CRENOLANIB	3	TNIK
SARACATINIB	3	TNIK
LINIFANIB	3	TNIK
ORANTINIB	3	TNIK
CANERTINIB	3	TNIK
BRIVANIB	3	TNIK
CEDIRANIB	3	TNIK
DOVITINIB	3	TNIK
LESTAURTINIB	3	TNIK
RUBOXISTAURIN	3	TNIK
DORAMAPIMOD	2	TNIK
FORETINIB	2	TNIK
CC-401	2	TNIK
SU-014813	2	TNIK

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
TNIK	257	Binding:257

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
TNIK	257

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

30 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)
PONATINIB	4	TNIK
LENVATINIB	4	TNIK
AXITINIB	4	TNIK
SORAFENIB	4	TNIK
NERATINIB	4	TNIK
PACRITINIB	4	TNIK
VANDETANIB	4	TNIK
BOSUTINIB	4	TNIK
PAZOPANIB	4	TNIK
NINTEDANIB	4	TNIK
SUNITINIB	4	TNIK
DASATINIB	4	TNIK
ERLOTINIB	4	TNIK
QUIZARTINIB	4	TNIK
MIDOSTAURIN	4	TNIK
GEFITINIB	4	TNIK
CRENOLANIB	3	TNIK
SARACATINIB	3	TNIK
LINIFANIB	3	TNIK
ORANTINIB	3	TNIK
CANERTINIB	3	TNIK
BRIVANIB	3	TNIK
CEDIRANIB	3	TNIK
DOVITINIB	3	TNIK
LESTAURTINIB	3	TNIK
RUBOXISTAURIN	3	TNIK
DORAMAPIMOD	2	TNIK
FORETINIB	2	TNIK
CC-401	2	TNIK
SU-014813	2	TNIK

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	TNIK
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.