Intellectual developmental disorder, autosomal dominant 72

Summary

Intellectual developmental disorder, autosomal dominant 72 (MONDO:0957397) is a disease caused by SRRM2 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: SRRM2 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 49

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual developmental disorder, autosomal dominant 72
Mondo ID	MONDO:0957397
OMIM	620439
Orphanet	652487
DOID	DOID:0061045
UMLS	C5830612
MedGen	1841248
GARD	0026821
Is cancer (heuristic)	no

Also known as: autosomal dominant intellectual developmental disorder-72 · developmental delay-overweight-facial dysmorphism-behavioral abnormalities syndrome · MRD72 · SRRM2-related neurodevelopmental disorder

Data availability: 49 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal dominant disease › intellectual disability, autosomal dominant › intellectual developmental disorder, autosomal dominant 72

Related subtypes (28): intellectual disability, autosomal dominant 1, intellectual disability, autosomal dominant 3, intellectual disability, autosomal dominant 4, intellectual disability, autosomal dominant 5, intellectual disability, autosomal dominant 6, intellectual disability, autosomal dominant 2, neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant, intellectual disability, autosomal dominant 9, intellectual disability, autosomal dominant 10, intellectual disability, autosomal dominant 11, intellectual disability, autosomal dominant 24, intellectual disability, autosomal dominant 38, intellectual disability, autosomal dominant 39, intellectual disability, autosomal dominant 40, intellectual disability, autosomal dominant 42, autosomal dominant non-syndromic intellectual disability, intellectual developmental disorder, autosomal dominant 65, intellectual developmental disorder, autosomal dominant 69, intellectual developmental disorder, autosomal dominant 66, intellectual developmental disorder, autosomal dominant 64, intellectual developmental disorder, autosomal dominant 67, intellectual developmental disorder, autosomal dominant 68, autosomal dominant syndromic intellectual disability, intellectual developmental disorder, autosomal dominant 70, intellectual developmental disorder, autosomal dominant 71, with behavioral abnormalities, intellectual developmental disorder, autosomal dominant 74, intellectual developmental disorder, autosomal dominant 75, intellectual developmental disorder, autosomal dominant 76

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

49 retrieved; paginated sample, class counts are floors:

16 pathogenic, 14 uncertain significance, 14 likely pathogenic, 3 conflicting classifications of pathogenicity, 2 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1321945	NM_016333.4(SRRM2):c.3346C>T (p.Gln1116Ter)	SRRM2	Pathogenic	criteria provided, single submitter
1321946	NM_016333.4(SRRM2):c.2970_2971del (p.Gly991fs)	SRRM2	Pathogenic	criteria provided, single submitter
1333013	NM_016333.4(SRRM2):c.4913C>G (p.Ser1638Ter)	SRRM2	Pathogenic	criteria provided, single submitter
1333022	NM_016333.4(SRRM2):c.6709dup (p.Ala2237fs)	SRRM2	Pathogenic	criteria provided, single submitter
1333023	NM_016333.4(SRRM2):c.6127C>T (p.Arg2043Ter)	SRRM2	Pathogenic	criteria provided, single submitter
1333024	NM_016333.4(SRRM2):c.4616C>A (p.Ser1539Ter)	SRRM2	Pathogenic	criteria provided, single submitter
1333025	NM_016333.4(SRRM2):c.2782_2785del (p.Arg928fs)	SRRM2	Pathogenic	criteria provided, multiple submitters, no conflicts
2498046	NM_016333.4(SRRM2):c.7748_7758del (p.Thr2583fs)	SRRM2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2691869	NM_016333.4(SRRM2):c.4583_4584del (p.Val1528fs)	SRRM2	Pathogenic	criteria provided, single submitter
3075954	NM_016333.4(SRRM2):c.4537del (p.Gln1513fs)	SRRM2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3358862	NM_016333.4(SRRM2):c.3399_3403del (p.Ser1136fs)	SRRM2	Pathogenic	criteria provided, single submitter
3359126	NM_016333.4(SRRM2):c.5653C>T (p.Arg1885Ter)	SRRM2	Pathogenic	criteria provided, single submitter
3775579	NM_016333.4(SRRM2):c.6007C>T (p.Arg2003Ter)	SRRM2	Pathogenic	criteria provided, single submitter
3900975	NM_016333.4(SRRM2):c.6528_6598del (p.Ala2177fs)	SRRM2	Pathogenic	criteria provided, single submitter
4294394	NM_016333.4(SRRM2):c.4056_4059del (p.Glu1353fs)	SRRM2	Pathogenic	criteria provided, single submitter
4531601	NM_016333.4(SRRM2):c.7246C>T (p.Gln2416Ter)	SRRM2	Pathogenic	criteria provided, single submitter
4796633	NM_016333.4(SRRM2):c.3215dup (p.Ser1073fs)	SRRM2	Pathogenic	criteria provided, single submitter
4813569	NM_016333.4(SRRM2):c.108C>G (p.Tyr36Ter)	SRRM2	Pathogenic	criteria provided, single submitter
3064119	NM_016333.4(SRRM2):c.1181dup (p.Ser395fs)	SRRM2	Likely pathogenic	criteria provided, single submitter
3358975	NM_016333.4(SRRM2):c.205C>T (p.Arg69Ter)	SRRM2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3359049	NM_016333.4(SRRM2):c.1585C>T (p.Gln529Ter)	SRRM2	Likely pathogenic	criteria provided, single submitter
3764727	NM_016333.4(SRRM2):c.1534C>T (p.Gln512Ter)	SRRM2	Likely pathogenic	criteria provided, single submitter
3775306	NM_016333.4(SRRM2):c.5059C>T (p.Arg1687Ter)	SRRM2	Likely pathogenic	criteria provided, single submitter
3775484	NM_016333.4(SRRM2):c.733C>T (p.Arg245Ter)	SRRM2	Likely pathogenic	criteria provided, single submitter
4076221	NM_016333.4(SRRM2):c.4082dup (p.Asn1361fs)	SRRM2	Likely pathogenic	criteria provided, single submitter
4280658	NM_016333.4(SRRM2):c.116_117dup (p.Glu40fs)	SRRM2	Likely pathogenic	criteria provided, single submitter
4291984	NM_016333.4(SRRM2):c.-31-2A>G	SRRM2	Likely pathogenic	criteria provided, single submitter
4292271	NM_016333.4(SRRM2):c.172del (p.Leu58fs)	SRRM2	Likely pathogenic	criteria provided, single submitter
4292601	NM_016333.4(SRRM2):c.673A>T (p.Lys225Ter)	SRRM2	Likely pathogenic	criteria provided, single submitter
4293574	NM_016333.4(SRRM2):c.5824dup (p.Thr1942fs)	SRRM2	Likely pathogenic	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
SRRM2	Definitive	Autosomal dominant	intellectual developmental disorder, autosomal dominant 72	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SRRM2	Orphanet:652487	Developmental delay-overweight-facial dysmorphism-behavioral abnormalities syndrome

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
SRRM2	HGNC:16639	ENSG00000167978	Q9UQ35	Serine/arginine repetitive matrix protein 2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SRRM2	Serine/arginine repetitive matrix protein 2	Required for pre-mRNA splicing as component of the spliceosome.

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)
SRRM2	Other/Unknown	no		mRNA_splic_Cwf21_dom, Spt5_C_dom, SRRM2_cwf21

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
right hemisphere of cerebellum	1
right lobe of thyroid gland	1
right uterine tube	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SRRM2	301	ubiquitous	marker	right uterine tube, right hemisphere of cerebellum, right lobe of thyroid gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SRRM2	3,507

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SRRM2	Q9UQ35	25

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. 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
mRNA Splicing	1	109.8×	0.024	SRRM2
mRNA Polyadenylation	1	87.8×	0.024	SRRM2
Processing of Capped Intron-Containing Pre-mRNA	1	82.2×	0.024	SRRM2
mRNA Splicing - Major Pathway	1	54.6×	0.024	SRRM2
Dengue Virus-Host Interactions	1	45.7×	0.024	SRRM2
Metabolism of RNA	1	41.7×	0.024	SRRM2

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
mRNA splicing, via spliceosome	1	91.6×	0.011	SRRM2

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · 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).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SRRM2	1	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	SRRM2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
SRRM2	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

1 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)
MOLIBRESIB	2	SRRM2

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	1	SRRM2
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.