Intellectual developmental disorder, autosomal recessive 79

Summary

Intellectual developmental disorder, autosomal recessive 79 (MONDO:0957288) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual developmental disorder, autosomal recessive 79
Mondo ID	MONDO:0957288
OMIM	620393
UMLS	C5830553
MedGen	1841189
GARD	0026812
Is cancer (heuristic)	no

Data availability: 3 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 developmental disorder, autosomal recessive 79

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 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 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

3 retrieved; paginated sample, class counts are floors:

3 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
2502915	NM_003292.3(TPR):c.6625C>T (p.Arg2209Ter)	TPR	Uncertain significance	criteria provided, single submitter
2502916	NM_003292.3(TPR):c.2610+5G>A	TPR	Uncertain significance	criteria provided, single submitter
4292046	NM_003292.3(TPR):c.1390-73dup	TPR	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 2 · 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
TPR	Limited	Autosomal recessive	intellectual developmental disorder, autosomal recessive 79	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TPR	Orphanet:146	Differentiated thyroid carcinoma
TPR	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
TPR	HGNC:12017	ENSG00000047410	P12270	Nucleoprotein TPR	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TPR	Nucleoprotein TPR	Component of the nuclear pore complex (NPC), a complex required for the trafficking across the nuclear envelope.

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)
TPR	Other/Unknown	no		Nucleoprot-TPR/MLP1-2_dom, Nucleoprot-TPR/MLP1_dom, NUA/TPR/MLP1-2-like_dom

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
cranial nerve II	1
endometrium epithelium	1
tendon of biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TPR	294	ubiquitous	marker	tendon of biceps brachii, endometrium epithelium, cranial nerve II

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TPR	3,018

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TPR	P12270	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 31. 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
IPs transport between nucleus and cytosol	1	380.7×	0.007	TPR
IP3 and IP4 transport between cytosol and nucleus	1	380.7×	0.007	TPR
IP6 and IP7 transport between cytosol and nucleus	1	380.7×	0.007	TPR
Transport of Ribonucleoproteins into the Host Nucleus	1	356.9×	0.007	TPR
Regulation of Glucokinase by Glucokinase Regulatory Protein	1	356.9×	0.007	TPR
Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC)	1	356.9×	0.007	TPR
NEP/NS2 Interacts with the Cellular Export Machinery	1	346.1×	0.007	TPR
Nuclear import of Rev protein	1	335.9×	0.007	TPR
Vpr-mediated nuclear import of PICs	1	335.9×	0.007	TPR
Transport of the SLBP independent Mature mRNA	1	326.3×	0.007	TPR
SUMOylation of SUMOylation proteins	1	326.3×	0.007	TPR
Transport of the SLBP Dependant Mature mRNA	1	317.2×	0.007	TPR
Rev-mediated nuclear export of HIV RNA	1	317.2×	0.007	TPR
Nuclear Pore Complex (NPC) Disassembly	1	308.6×	0.007	TPR
SUMOylation of ubiquitinylation proteins	1	292.8×	0.007	TPR
NS1 Mediated Effects on Host Pathways	1	285.5×	0.007	TPR
Transport of Mature mRNA Derived from an Intronless Transcript	1	271.9×	0.007	TPR
Viral Messenger RNA Synthesis	1	259.6×	0.007	TPR
SUMOylation of DNA replication proteins	1	248.3×	0.007	TPR
SUMOylation of RNA binding proteins	1	237.9×	0.007	TPR
snRNP Assembly	1	211.5×	0.007	TPR
tRNA processing in the nucleus	1	196.9×	0.007	TPR
SUMOylation of chromatin organization proteins	1	158.6×	0.008	TPR
Transport of Mature mRNA derived from an Intron-Containing Transcript	1	152.3×	0.008	TPR
ISG15 antiviral mechanism	1	150.3×	0.008	TPR
Signaling by ALK fusions and activated point mutants	1	150.3×	0.008	TPR
SUMOylation of DNA damage response and repair proteins	1	146.4×	0.008	TPR
Regulation of HSF1-mediated heat shock response	1	139.3×	0.008	TPR
HCMV Late Events	1	98.5×	0.011	TPR
SARS-CoV-2 activates/modulates innate and adaptive immune responses	1	89.2×	0.012	TPR

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
regulation of mitotic sister chromatid separation	1	16852.0×	7e-04	TPR
mRNA export from nucleus in response to heat stress	1	16852.0×	7e-04	TPR
positive regulation of heterochromatin formation	1	8426.0×	8e-04	TPR
RNA import into nucleus	1	5617.3×	8e-04	TPR
negative regulation of RNA export from nucleus	1	5617.3×	8e-04	TPR
response to epidermal growth factor	1	3370.4×	0.001	TPR
nuclear pore organization	1	2106.5×	0.002	TPR
cellular response to interferon-alpha	1	1532.0×	0.002	TPR
positive regulation of mitotic cell cycle spindle assembly checkpoint	1	1532.0×	0.002	TPR
RNA export from nucleus	1	936.2×	0.002	TPR
negative regulation of translational initiation	1	887.0×	0.002	TPR
positive regulation of protein export from nucleus	1	802.5×	0.002	TPR
regulation of mitotic spindle assembly	1	732.7×	0.002	TPR
positive regulation of intracellular protein transport	1	674.1×	0.002	TPR
mitotic spindle assembly checkpoint signaling	1	561.7×	0.003	TPR
positive regulation of protein import into nucleus	1	421.3×	0.003	TPR
nucleocytoplasmic transport	1	391.9×	0.003	TPR
cellular response to heat	1	343.9×	0.004	TPR
mRNA export from nucleus	1	295.6×	0.004	TPR
regulation of protein localization	1	205.5×	0.006	TPR
protein import into nucleus	1	144.0×	0.008	TPR
cell division	1	46.2×	0.023	TPR
negative regulation of transcription by RNA polymerase II	1	17.7×	0.056	TPR

Therapeutics

Drug target analysis

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

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

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TPR	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
TPR	7	Binding:7

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	TPR

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)
TPR	7	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.