Intellectual disability, autosomal recessive 27

Summary

Intellectual disability, autosomal recessive 27 (MONDO:0013702) is a disease caused by LINS1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: LINS1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 46

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual disability, autosomal recessive 27
Mondo ID	MONDO:0013702
OMIM	614340
DOID	DOID:0081193
UMLS	C3280538
MedGen	482168
GARD	0022555
Is cancer (heuristic)	no

Also known as: autosomal recessive non-syndromic intellectual disability caused by mutation in LINS1 · intellectual developmental disorder, autosomal recessive 27 · intellectual disability, autosomal recessive 27 · intellectual disability, autosomal recessive type 27 · LINS1 autosomal recessive non-syndromic intellectual disability · mental retardation, autosomal recessive 27 · mental retardation, autosomal recessive type 27 · MRT27

Data availability: 46 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 27

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 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

46 retrieved; paginated sample, class counts are floors:

22 uncertain significance, 14 likely pathogenic, 5 pathogenic, 3 conflicting classifications of pathogenicity, 1 likely benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
120182	NM_001040616.3(LINS1):c.985_988del (p.His328_His329insTer)	LINS1	Pathogenic	no assertion criteria provided
120183	NM_001040616.3(LINS1):c.1219_1222+1del	LINS1	Pathogenic	criteria provided, single submitter
280510	NM_001040616.3(LINS1):c.1178T>G (p.Leu393Ter)	LINS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3771635	NM_001040616.3(LINS1):c.982_985del (p.His328fs)	LINS1	Pathogenic	criteria provided, multiple submitters, no conflicts
4537023	NM_001040616.3(LINS1):c.1460del (p.Asn487fs)	LINS1	Pathogenic	criteria provided, single submitter
800811	NM_001040616.3(LINS1):c.717C>A (p.Cys239Ter)	LINS1	Pathogenic	criteria provided, single submitter
1333602	NM_001040616.3(LINS1):c.1424_1425del (p.Gln475fs)	LINS1	Likely pathogenic	criteria provided, single submitter
1679222	NM_001040616.3(LINS1):c.1432G>T (p.Glu478Ter)	LINS1	Likely pathogenic	criteria provided, single submitter
1684037	NM_001040616.3(LINS1):c.1727_1736del (p.Arg576fs)	LINS1	Likely pathogenic	criteria provided, single submitter
2431402	NM_001040616.3(LINS1):c.1921_1923delinsAC (p.Glu641fs)	LINS1	Likely pathogenic	criteria provided, single submitter
2441184	NM_001040616.3(LINS1):c.1222+2T>C	LINS1	Likely pathogenic	criteria provided, single submitter
2682503	NM_001040616.3(LINS1):c.631+1G>A	LINS1	Likely pathogenic	criteria provided, single submitter
2683927	NM_001040616.3(LINS1):c.1605G>A (p.Trp535Ter)	LINS1	Likely pathogenic	criteria provided, single submitter
3065021	NM_001040616.3(LINS1):c.2185A>T (p.Lys729Ter)	LINS1	Likely pathogenic	criteria provided, single submitter
3257737	NM_001040616.3(LINS1):c.2134del (p.Arg711_Ile712insTer)	LINS1	Likely pathogenic	criteria provided, single submitter
374936	NM_001040616.3(LINS1):c.937G>A (p.Glu313Lys)	LINS1	Likely pathogenic	no assertion criteria provided
4526452	NM_001040616.3(LINS1):c.497T>G (p.Leu166Ter)	LINS1	Likely pathogenic	no assertion criteria provided
978100	NM_001040616.3(LINS1):c.490-1G>C	LINS1	Likely pathogenic	criteria provided, single submitter
982564	NM_001040616.3(LINS1):c.597del (p.Glu200fs)	LINS1	Likely pathogenic	criteria provided, single submitter
982565	NM_001040616.3(LINS1):c.557_558del (p.Lys186fs)	LINS1	Likely pathogenic	criteria provided, single submitter
445417	NM_001040616.3(LINS1):c.431del (p.Leu144fs)	LINS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
588781	NM_001040616.3(LINS1):c.1993G>A (p.Gly665Arg)	LINS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
598240	NM_001040616.3(LINS1):c.304del (p.Arg102fs)	LINS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1028987	NM_001040616.3(LINS1):c.1481T>C (p.Ile494Thr)	LINS1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1030057	NM_001040616.3(LINS1):c.2032C>T (p.Pro678Ser)	LINS1	Uncertain significance	criteria provided, single submitter
1031758	NM_001040616.3(LINS1):c.1013C>T (p.Ala338Val)	LINS1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1031759	NM_001040616.3(LINS1):c.134C>T (p.Thr45Ile)	LINS1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1031760	NM_001040616.3(LINS1):c.1487T>C (p.Leu496Ser)	LINS1	Uncertain significance	criteria provided, single submitter
1031761	NM_001040616.3(LINS1):c.1826C>G (p.Ala609Gly)	LINS1	Uncertain significance	criteria provided, single submitter
1031762	NM_001040616.3(LINS1):c.2004G>C (p.Arg668Ser)	LINS1	Uncertain significance	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
LINS1	Strong	Autosomal recessive	intellectual disability, autosomal recessive 27	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
LINS1	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
LINS1	HGNC:30922	ENSG00000140471	Q8NG48	Protein Lines homolog 1	gencc,clinvar

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)
LINS1	Other/Unknown	no		Protein_Lines, Lines_C, LINES_N

Expression context

Cohort genes with no expression data: 0.

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
epithelium of nasopharynx	1
gingival epithelium	1
nasopharynx	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
LINS1	258	ubiquitous	yes	epithelium of nasopharynx, nasopharynx, gingival epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LINS1	373

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
LINS1	Q8NG48	72.44

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
cognition	1	285.6×	0.004	LINS1

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
LINS1	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	LINS1

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)
LINS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.