SRRM2

Summary

SRRM2 (serine/arginine repetitive matrix 2, HGNC:16639) is a protein-coding gene on chromosome 16p13.3, encoding Serine/arginine repetitive matrix protein 2 (Q9UQ35). Required for pre-mRNA splicing as component of the spliceosome. It is a selective cancer dependency (DepMap: 40.1% of cell lines) and haploinsufficient (ClinGen: sufficient evidence).

Enables C2H2 zinc finger domain binding activity. Involved in mRNA splicing, via spliceosome. Located in Cajal body and nuclear speck. Part of U2-type catalytic step 2 spliceosome and U2-type precatalytic spliceosome. Implicated in autosomal dominant intellectual developmental disorder 72. Biomarker of Parkinson’s disease.

Source: NCBI Gene 23524 — RefSeq curated summary.

At a glance

• Gene–disease (curated): intellectual developmental disorder, autosomal dominant 72 (Definitive, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 1,135 total — 43 pathogenic, 22 likely-pathogenic
• Phenotypes (HPO): 35
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 40.1% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_016333

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16639
Approved symbol	SRRM2
Name	serine/arginine repetitive matrix 2
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Aliases	SRm300, SRL300, KIAA0324, Cwc21
Ensembl gene	ENSG00000167978
Ensembl biotype	protein_coding
OMIM	606032
Entrez	23524

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 13 retained_intron, 6 protein_coding, 4 protein_coding_CDS_not_defined, 3 nonsense_mediated_decay

ENST00000301740, ENST00000570539, ENST00000570655, ENST00000570705, ENST00000570971, ENST00000571041, ENST00000571372, ENST00000571378, ENST00000572721, ENST00000572883, ENST00000572952, ENST00000573311, ENST00000573451, ENST00000573498, ENST00000573583, ENST00000573692, ENST00000574331, ENST00000574340, ENST00000574593, ENST00000575009, ENST00000575870, ENST00000576674, ENST00000576878, ENST00000576894, ENST00000576924, ENST00000704117

RefSeq mRNA: 1 — MANE Select: NM_016333 NM_016333

CCDS: CCDS32373

Canonical transcript exons

ENST00000301740 — 15 exons

Exon	Start	End
ENSE00002632931	2761561	2768261
ENSE00002668900	2752638	2752846
ENSE00003305031	2770858	2771412
ENSE00003477485	2758985	2759047
ENSE00003480532	2759352	2759402
ENSE00003481438	2759569	2759661
ENSE00003489626	2760301	2760499
ENSE00003503462	2758470	2758547
ENSE00003556335	2756334	2756606
ENSE00003618232	2757472	2757579
ENSE00003641261	2759140	2759172
ENSE00003738367	2757781	2757945
ENSE00003990794	2770352	2770465
ENSE00003990795	2770604	2770717
ENSE00003990796	2768997	2769284

Expression profiles

Bgee: expression breadth ubiquitous, 301 present calls, max score 99.81.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 151.1457 / max 5280.5575, expressed in 1826 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
152267	147.9000	1826
152294	0.9974	683
152295	0.7190	381
152274	0.5692	292
152272	0.4352	195
152296	0.3289	167
152298	0.1959	75

Top tissues by expression

302 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	99.81	gold quality
right hemisphere of cerebellum	UBERON:0014890	99.79	gold quality
right lobe of thyroid gland	UBERON:0001119	99.72	gold quality
cerebellar hemisphere	UBERON:0002245	99.69	gold quality
small intestine Peyer’s patch	UBERON:0003454	99.69	gold quality
endocervix	UBERON:0000458	99.68	gold quality
left lobe of thyroid gland	UBERON:0001120	99.68	gold quality
body of uterus	UBERON:0009853	99.68	gold quality
nerve	UBERON:0001021	99.66	gold quality
tibial nerve	UBERON:0001323	99.66	gold quality
cerebellar cortex	UBERON:0002129	99.66	gold quality
metanephros cortex	UBERON:0010533	99.66	gold quality
colonic epithelium	UBERON:0000397	99.65	gold quality
fundus of stomach	UBERON:0001160	99.65	gold quality
body of stomach	UBERON:0001161	99.63	gold quality
right ovary	UBERON:0002118	99.63	gold quality
left ovary	UBERON:0002119	99.63	gold quality
right adrenal gland cortex	UBERON:0035827	99.62	gold quality
transverse colon	UBERON:0001157	99.60	gold quality
pylorus	UBERON:0001166	99.60	gold quality
right adrenal gland	UBERON:0001233	99.60	gold quality
left uterine tube	UBERON:0001303	99.60	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.60	gold quality
granulocyte	CL:0000094	99.59	gold quality
adenohypophysis	UBERON:0002196	99.59	gold quality
left testis	UBERON:0004533	99.59	gold quality
minor salivary gland	UBERON:0001830	99.58	gold quality
right testis	UBERON:0004534	99.58	gold quality
upper lobe of left lung	UBERON:0008952	99.58	gold quality
ectocervix	UBERON:0012249	99.58	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-10855	yes	1145.17
E-MTAB-8205	yes	514.61
E-MTAB-8060	no	624.64
E-CURD-97	no	162.36
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F4

miRNA regulators (miRDB)

43 targeting SRRM2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-5003-5P	99.61	69.13	1624
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-4480	99.42	66.02	735
HSA-MIR-7109-5P	99.18	66.13	1057
HSA-MIR-6829-5P	98.86	65.12	1480

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 40.1% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 10)

• results suggest multiple functions for Cwc21/SRm300 in the splicing process, including an important role in the activation of splicing in association with Isy1. (PMID:19789211)
• demonstrate that SRm300, the only serine arginine-related protein known to be at the core of human catalytic spliceosomes, is a functional ortholog of Cwc21p, also interacting directly with Prp8p and Snu114p. (PMID:19854871)
• Data show that the consistent dysregulation of the RNA splicing factor SRRM2 in two different PD neuronal sources and in PD blood makes SRRM2 a strong candidate gene for PD and draws attention to the role of RNA splicing in the disease. (PMID:20161708)
• The S346F mutation in SRRM2 predisposes to papillary thyroid carcinoma by affecting alternative splicing of unidentified downstream target genes. (PMID:26135620)
• cellular complexes comprising cactin, DHX8 and SRRM2 sustain precise chromosome segregation, genome stability and cell proliferation by allowing faithful splicing of specific pre-mRNAs. (PMID:28062851)
• SON and SRRM2 are essential for nuclear speckle formation. (PMID:33095160)
• A compound downregulation of SRRM2 and miR-27a-3p with upregulation of miR-27b-3p in PBMCs of Parkinson’s patients is associated with the early stage onset of disease. (PMID:33171483)
• Loss-of-function variants in SRRM2 cause a neurodevelopmental disorder. (PMID:35567594)
• SRRM2 organizes splicing condensates to regulate alternative splicing. (PMID:35929045)
• SRRM2 may be a potential biomarker and immunotherapy target for multiple myeloma: a real-world study based on flow cytometry detection. (PMID:38289482)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Srrm2	ENSMUSG00000039218
rattus_norvegicus	Srrm2	ENSRNOG00000058561

Paralogs (1): MUC12 (ENSG00000205277)

Protein

Protein identifiers

Serine/arginine repetitive matrix protein 2 — Q9UQ35 (reviewed: Q9UQ35)

Alternative names: 300 kDa nuclear matrix antigen, Serine/arginine-rich splicing factor-related nuclear matrix protein of 300 kDa, Splicing coactivator subunit SRm300, Tax-responsive enhancer element-binding protein 803

All UniProt accessions (10): A0A087X1W1, A0A140VK53, A0A994J493, Q9UQ35, I3L0N7, I3L182, I3L1I8, I3L3Q8, I3L4D8, I3L4U6

UniProt curated annotations — full annotation on UniProt →

Function. Required for pre-mRNA splicing as component of the spliceosome. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs.

Subunit / interactions. Component of pre-catalytic, catalytic and post-catalytic spliceosome complexes. Found in a pre-mRNA splicing complex with SFRS4, SFRS5, SNRP70, SNRPA1, SRRM1 and SRRM2. Component of the minor spliceosome, which splices U12-type introns. Interacts with DHX8. Interacts with CACTIN.

Subcellular location. Nucleus. Nucleus speckle.

Tissue specificity. Expressed in liver, placenta, and white blood cells.

Disease relevance. Intellectual developmental disorder, autosomal dominant 72 (MRD72) [MIM:620439] An autosomal dominant disorder characterized by mild developmental delay and intellectual disability, predominant speech delay, autistic or attention deficit-hyperactivity disorder features, overfriendliness, generalized hypotonia, overweight, and dysmorphic facial features. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. Can functionally substitute for CWC12 in yeast.

Similarity. Belongs to the CWC21 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9UQ35-1	1	yes
Q9UQ35-2	2
Q9UQ35-3	3

RefSeq proteins (1): NP_057417* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013170	mRNA_splic_Cwf21_dom	Domain
IPR024945	Spt5_C_dom	Domain
IPR047490	SRRM2_cwf21	Domain
IPR051372	CWC21	Family

Pfam: PF08312

UniProt features (376 total): modified residue 282, compositionally biased region 57, sequence variant 11, sequence conflict 6, region of interest 4, splice variant 4, cross-link 3, helix 3, turn 2, strand 2, chain 1, coiled-coil region 1

Structure

Experimental structures (PDB)

25 structures.

PDB	Method	Resolution (Å)
8C6J	ELECTRON MICROSCOPY	2.8
7DVQ	ELECTRON MICROSCOPY	2.89
6ICZ	ELECTRON MICROSCOPY	3
8I0R	ELECTRON MICROSCOPY	3
8I0T	ELECTRON MICROSCOPY	3
8I0V	ELECTRON MICROSCOPY	3
7QTT	ELECTRON MICROSCOPY	3.1
6QDV	ELECTRON MICROSCOPY	3.3
8I0U	ELECTRON MICROSCOPY	3.3
9FMD	ELECTRON MICROSCOPY	3.3
6FF4	ELECTRON MICROSCOPY	3.4
6ZYM	ELECTRON MICROSCOPY	3.4
8I0W	ELECTRON MICROSCOPY	3.4
5XJC	ELECTRON MICROSCOPY	3.6
7W59	ELECTRON MICROSCOPY	3.6
7W5A	ELECTRON MICROSCOPY	3.6
5YZG	ELECTRON MICROSCOPY	4.1
8I0S	ELECTRON MICROSCOPY	4.2
7W5B	ELECTRON MICROSCOPY	4.3
6FF7	ELECTRON MICROSCOPY	4.5
7A5P	ELECTRON MICROSCOPY	5
5Z56	ELECTRON MICROSCOPY	5.1
5MQF	ELECTRON MICROSCOPY	5.9
8CH6	ELECTRON MICROSCOPY	5.9
5Z57	ELECTRON MICROSCOPY	6.5

Predicted structure (AlphaFold)

No AlphaFold model available for Q9UQ35 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (285): 534, 536, 543, 702, 704, 706, 778, 780, 783, 846, 854, 856, 857, 864, 866, 871, 875, 876, 908, 935 …

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-72163	mRNA Splicing - Major Pathway
R-HSA-9770562	mRNA Polyadenylation
R-HSA-9918481	Dengue Virus-Host Interactions
R-HSA-72172	mRNA Splicing
R-HSA-72203	Processing of Capped Intron-Containing Pre-mRNA
R-HSA-8953854	Metabolism of RNA

MSigDB gene sets: 278 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, AHRARNT_01, TGCGCANK_UNKNOWN, GOZGIT_ESR1_TARGETS_DN, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP, MODULE_128, MODULE_16, BILD_HRAS_ONCOGENIC_SIGNATURE, BLALOCK_ALZHEIMERS_DISEASE_UP, REACTOME_MRNA_3_END_PROCESSING, TGCTGAY_UNKNOWN, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, CCTGTGA_MIR513, KINSEY_TARGETS_OF_EWSR1_FLII_FUSION_DN, GOBP_RNA_SPLICING

GO Biological Process (3): mRNA splicing, via spliceosome (GO:0000398), mRNA processing (GO:0006397), RNA splicing (GO:0008380)

GO Molecular Function (4): RNA binding (GO:0003723), mRNA binding (GO:0003729), C2H2 zinc finger domain binding (GO:0070742), protein binding (GO:0005515)

GO Cellular Component (8): nucleus (GO:0005634), nucleoplasm (GO:0005654), Cajal body (GO:0015030), nuclear speck (GO:0016607), U2-type precatalytic spliceosome (GO:0071005), U2-type catalytic step 2 spliceosome (GO:0071007), catalytic step 2 spliceosome (GO:0071013), spliceosomal complex (GO:0005681)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
mRNA Splicing	1
mRNA 3’-end processing	1
Dengue Virus Infection	1
Processing of Capped Intron-Containing Pre-mRNA	1
Metabolism of RNA	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA processing	2
nuclear ribonucleoprotein granule	2
U2-type spliceosomal complex	2
U2 snRNP	2
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
mRNA metabolic process	1
nucleic acid binding	1
RNA binding	1
protein domain specific binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
U1 snRNP	1
U4/U6 x U5 tri-snRNP complex	1
precatalytic spliceosome	1
U6 snRNP	1
catalytic step 2 spliceosome	1
Prp19 complex	1
spliceosomal complex	1
U5 snRNP	1
catalytic complex	1
nuclear protein-containing complex	1
ribonucleoprotein complex	1

Protein interactions and networks

STRING

2542 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SRRM2	SRRM1	Q8IYB3	990
SRRM2	EFTUD2	Q15029	916
SRRM2	RBM25	P49756	882
SRRM2	SRSF4	Q08170	824
SRRM2	CWC22	Q9HCG8	824
SRRM2	CDC5L	Q99459	777
SRRM2	CWC25	Q9NXE8	728
SRRM2	SF3A2	Q15428	643
SRRM2	SRRM4	A7MD48	622
SRRM2	CDC40	O60508	613
SRRM2	ACIN1	Q9UKV3	600
SRRM2	YJU2	Q9BW85	586
SRRM2	PNISR	Q8TF01	585
SRRM2	SNRNP200	O75643	564
SRRM2	HNRNPM	P52272	563

IntAct

324 interactions, top by confidence:

A	B	Type	Score
PTPN3	YWHAQ	psi-mi:“MI:2364”(proximity)	0.850
HIF1AN	APBA3	psi-mi:“MI:0914”(association)	0.850
ATXN2	PABPC1	psi-mi:“MI:0915”(physical association)	0.820
YWHAH	FAM83G	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
ZNF398	ZNF282	psi-mi:“MI:0914”(association)	0.710
PTK2	TGFB1I1	psi-mi:“MI:0914”(association)	0.680
PTPN3	MCC	psi-mi:“MI:0914”(association)	0.660
PNN	CASC3	psi-mi:“MI:0914”(association)	0.640
CAMKV	AP3B1	psi-mi:“MI:0914”(association)	0.640
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
SF3B1	SAP18	psi-mi:“MI:0914”(association)	0.640
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
PTPN3	ACOT8	psi-mi:“MI:0914”(association)	0.590
NUAK1	SRRM2	psi-mi:“MI:0915”(physical association)	0.560
ILK	HAX1	psi-mi:“MI:0914”(association)	0.530
EBNA-LP	HAX1	psi-mi:“MI:0914”(association)	0.530
MAPT	KIF2A	psi-mi:“MI:0914”(association)	0.530
PIP4K2A	AP3B1	psi-mi:“MI:0914”(association)	0.530
XAGE1A	THAP12	psi-mi:“MI:0914”(association)	0.530
PES1	AP3B1	psi-mi:“MI:0914”(association)	0.530
EPB41L2	AP3B1	psi-mi:“MI:0914”(association)	0.530
FAM9A	AP3B1	psi-mi:“MI:0914”(association)	0.530
MDK	SETD1A	psi-mi:“MI:0914”(association)	0.530
SREK1IP1	KPNA5	psi-mi:“MI:0914”(association)	0.530
SNIP1	CASC3	psi-mi:“MI:0914”(association)	0.530
ZC3H18	AQR	psi-mi:“MI:0914”(association)	0.530
DDX41	NOS1AP	psi-mi:“MI:0914”(association)	0.530

BioGRID (641): SRRM2 (Affinity Capture-MS), SRRM2 (Affinity Capture-MS), SRRM2 (Affinity Capture-MS), SRRM2 (Affinity Capture-MS), SRRM2 (Affinity Capture-MS), SRRM2 (Affinity Capture-MS), SRRM2 (Affinity Capture-MS), SRRM2 (Affinity Capture-MS), SRRM2 (Affinity Capture-MS), SRRM2 (Affinity Capture-MS), SRRM2 (Affinity Capture-MS), SRRM2 (Affinity Capture-MS), SRRM2 (Affinity Capture-MS), SRRM2 (Affinity Capture-MS), SRRM2 (Affinity Capture-MS)

ESM2 similar proteins: A0P8Z5, A2AJT4, A6NNA2, A7MD48, F1LR10, O88573, P0CB65, P51825, P51826, P51827, Q14241, Q2KJH5, Q2T9Y0, Q569Z6, Q5BJ39, Q5M7V8, Q5PPJ2, Q5RD75, Q5T6C5, Q5VUA4, Q63187, Q6QZN6, Q6ZPR1, Q80WV7, Q80Z37, Q8BKA3, Q8BM65, Q8BTI8, Q8BZX4, Q8CB77, Q8K019, Q8TF01, Q93075, Q96B23, Q96IZ7, Q96RL1, Q99PP2, Q9BW71, Q9DBU6, Q9ERQ3

Diamond homologs: A6NNA2, Q5AP89, Q6C0M9, Q80WV7, Q8BTI8, Q9U213, Q9UQ35, O14161, P0CM94, P0CM95, Q4IB70, Q4P0G6, Q4WDD0, Q751G9, Q7RYH7, Q03375, Q6BWB8, Q6FRM6, Q6CVR3, A7MD48, P0CB65, Q8BKA3

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 229 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	5	22.4×	1e-04
mRNA Splicing	15	11.0×	2e-09
AURKA Activation by TPX2	10	10.2×	7e-06
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	5	10.0×	3e-03
Intrinsic Pathway for Apoptosis	5	9.8×	4e-03
Loss of Nlp from mitotic centrosomes	9	9.5×	3e-05
Loss of proteins required for interphase microtubule organization from the centrosome	9	9.5×	3e-05
Regulation of PLK1 Activity at G2/M Transition	10	8.5×	3e-05

GO biological processes:

GO term	Partners	Fold	FDR
U2-type prespliceosome assembly	5	15.8×	6e-03
spliceosomal complex assembly	5	15.3×	6e-03
mRNA splicing, via spliceosome	21	9.8×	5e-12
RNA splicing	12	5.4×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

1135 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	43
Likely pathogenic	22
Uncertain significance	809
Likely benign	181
Benign	20

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1321945	NM_016333.4(SRRM2):c.3346C>T (p.Gln1116Ter)	Pathogenic
1321946	NM_016333.4(SRRM2):c.2970_2971del (p.Gly991fs)	Pathogenic
1333013	NM_016333.4(SRRM2):c.4913C>G (p.Ser1638Ter)	Pathogenic
1333014	NM_016333.4(SRRM2):c.4200_4203dup (p.Ile1402fs)	Pathogenic
1333015	NM_016333.4(SRRM2):c.3426_3427del (p.Ser1143fs)	Pathogenic
1333016	NM_016333.4(SRRM2):c.1882C>T (p.Arg628Ter)	Pathogenic
1333017	NM_016333.4(SRRM2):c.5074C>T (p.Arg1692Ter)	Pathogenic
1333018	NM_016333.4(SRRM2):c.5410_5411dup (p.Ser1804fs)	Pathogenic
1333019	NM_016333.4(SRRM2):c.6042_6043del (p.Arg2015fs)	Pathogenic
1333020	NM_016333.4(SRRM2):c.58C>T (p.Gln20Ter)	Pathogenic
1333021	NM_016333.4(SRRM2):c.2214_2215del (p.Arg739fs)	Pathogenic
1333022	NM_016333.4(SRRM2):c.6709dup (p.Ala2237fs)	Pathogenic
1333023	NM_016333.4(SRRM2):c.6127C>T (p.Arg2043Ter)	Pathogenic
1333024	NM_016333.4(SRRM2):c.4616C>A (p.Ser1539Ter)	Pathogenic
1333025	NM_016333.4(SRRM2):c.2782_2785del (p.Arg928fs)	Pathogenic
1333026	NM_016333.4(SRRM2):c.4528_4529del (p.Leu1510fs)	Pathogenic
1333027	NM_016333.4(SRRM2):c.4512_4578del (p.Asn1506fs)	Pathogenic
1333028	NM_016333.4(SRRM2):c.7254_7257del (p.Met2419fs)	Pathogenic
1333029	NM_016333.4(SRRM2):c.6265C>T (p.Arg2089Ter)	Pathogenic
2691869	NM_016333.4(SRRM2):c.4583_4584del (p.Val1528fs)	Pathogenic
2785579	NM_016333.4(SRRM2):c.136G>T (p.Glu46Ter)	Pathogenic
2959342	NM_016333.4(SRRM2):c.2783_2784del (p.Arg928fs)	Pathogenic
3322712	NM_016333.4(SRRM2):c.8064_8065del (p.Arg2689fs)	Pathogenic
3342659	NM_016333.4(SRRM2):c.657-1G>C	Pathogenic
3358862	NM_016333.4(SRRM2):c.3399_3403del (p.Ser1136fs)	Pathogenic
3359126	NM_016333.4(SRRM2):c.5653C>T (p.Arg1885Ter)	Pathogenic
3449525	NM_016333.4(SRRM2):c.838C>T (p.Arg280Ter)	Pathogenic
3449532	NM_016333.4(SRRM2):c.922dup (p.Ala308fs)	Pathogenic
3449536	NM_016333.4(SRRM2):c.6097C>T (p.Arg2033Ter)	Pathogenic
3449578	NM_016333.4(SRRM2):c.5506C>T (p.Arg1836Ter)	Pathogenic

SpliceAI

2292 predictions. Top by Δscore:

Variant	Effect	Δscore
16:2756329:CTCAG:C	acceptor_loss	1.0000
16:2756331:CAGGA:C	acceptor_loss	1.0000
16:2756332:A:AC	acceptor_loss	1.0000
16:2756332:A:AG	acceptor_gain	1.0000
16:2756332:AG:A	acceptor_gain	1.0000
16:2756333:G:GT	acceptor_gain	1.0000
16:2756333:G:T	acceptor_loss	1.0000
16:2756333:GG:G	acceptor_gain	1.0000
16:2756333:GGA:G	acceptor_gain	1.0000
16:2756333:GGAGC:G	acceptor_gain	1.0000
16:2756584:G:GT	donor_gain	1.0000
16:2756587:G:GT	donor_gain	1.0000
16:2756588:A:T	donor_gain	1.0000
16:2756590:A:G	donor_gain	1.0000
16:2756596:G:GT	donor_gain	1.0000
16:2756596:G:T	donor_gain	1.0000
16:2756603:AGGGG:A	donor_loss	1.0000
16:2756604:GGG:G	donor_gain	1.0000
16:2756605:GG:G	donor_gain	1.0000
16:2756605:GGG:G	donor_gain	1.0000
16:2756605:GGGTG:G	donor_loss	1.0000
16:2756606:GG:G	donor_gain	1.0000
16:2756606:GGT:G	donor_loss	1.0000
16:2756607:GTG:G	donor_loss	1.0000
16:2756608:T:G	donor_loss	1.0000
16:2756612:G:GT	donor_gain	1.0000
16:2757471:GGTAC:G	acceptor_gain	1.0000
16:2757533:G:GT	donor_gain	1.0000
16:2757554:G:GT	donor_gain	1.0000
16:2757578:GC:G	donor_gain	1.0000

AlphaMissense

17212 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:2756384:T:C	L7P	1.000
16:2756534:T:A	I57N	1.000
16:2756534:T:C	I57T	1.000
16:2756534:T:G	I57S	1.000
16:2756542:C:G	H60D	1.000
16:2756549:G:C	R62P	1.000
16:2756555:G:C	R64P	1.000
16:2756567:T:C	L68P	1.000
16:2756572:T:C	C70R	1.000
16:2756574:C:G	C70W	1.000
16:2756576:T:C	L71P	1.000
16:2756582:T:C	L73P	1.000
16:2756594:T:C	M77T	1.000
16:2757509:T:C	F94L	1.000
16:2757510:T:C	F94S	1.000
16:2757511:T:A	F94L	1.000
16:2757511:T:G	F94L	1.000
16:2757513:G:C	R95P	1.000
16:2757522:T:C	L98S	1.000
16:2757834:T:A	L135H	1.000
16:2757834:T:C	L135P	1.000
16:2757846:T:C	F139S	1.000
16:2757852:T:C	I141T	1.000
16:2757852:T:G	I141S	1.000
16:2756368:T:C	Y2H	0.999
16:2756369:A:G	Y2C	0.999
16:2756373:C:A	N3K	0.999
16:2756373:C:G	N3K	0.999
16:2756374:G:A	G4R	0.999
16:2756374:G:C	G4R	0.999

dbSNP variants (sampled 300 via entrez): RS1000029672 (16:2753336 C>A,T), RS1000103778 (16:2756368 TACAACGG>T), RS1000177608 (16:2769008 C>G,T), RS1000219278 (16:2756221 T>C), RS1000287967 (16:2764782 A>T), RS1000333278 (16:2753017 C>A,T), RS1000530222 (16:2767654 T>C), RS1000548313 (16:2769581 A>G), RS1000549262 (16:2753412 T>A,G), RS1000636142 (16:2768710 C>T), RS1000705525 (16:2771078 G>C,T), RS1001114026 (16:2757352 G>A,C), RS1001353143 (16:2755887 G>A,C,T), RS1001441353 (16:2750762 A>G), RS1001454949 (16:2753498 G>A)

Disease associations

OMIM: gene MIM:606032 | disease phenotypes: MIM:620439

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual developmental disorder, autosomal dominant 72	Definitive	Autosomal dominant

Mondo (2): neurodevelopmental disorder (MONDO:0700092), intellectual developmental disorder, autosomal dominant 72 (MONDO:0957397)

Orphanet (1): Developmental delay-overweight-facial dysmorphism-behavioral abnormalities syndrome (Orphanet:652487)

HPO phenotypes

35 total (30 of 35 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000049	Shawl scrotum
HP:0000054	Micropenis
HP:0000089	Renal hypoplasia
HP:0000098	Tall stature
HP:0000219	Thin upper lip vermilion
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000286	Epicanthus
HP:0000297	Facial hypotonia
HP:0000319	Smooth philtrum
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000414	Bulbous nose
HP:0000470	Short neck
HP:0000486	Strabismus
HP:0000490	Deeply set eye
HP:0000540	Hypermetropia
HP:0000729	Autistic behavior
HP:0000739	Anxiety
HP:0000750	Delayed speech and language development
HP:0001169	Broad palm
HP:0001252	Hypotonia
HP:0001256	Mild intellectual disability
HP:0001263	Global developmental delay
HP:0001513	Obesity
HP:0002414	Spina bifida
HP:0002591	Polyphagia
HP:0003593	Infantile onset
HP:0007018	Attention deficit hyperactivity disorder

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST008839_101	Height	7.000000e-16
GCST009936_12	Venous thromboembolism	9.000000e-06

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066164 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.70	IC50	20	nM	MOLIBRESIB
7.64	Kd	23	nM	MOLIBRESIB

PubChem BioAssay actives

2 with measured affinity, of 7 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178453: Inhibition of SRRM2 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	0.0200	uM

CTD chemical–gene interactions

64 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	affects expression, increases abundance, increases expression	3
Arsenic	affects methylation, affects cotreatment, decreases expression, increases abundance, increases expression	3
Dronabinol	increases expression	3
Valproic Acid	decreases expression	3
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	2
cobaltous chloride	decreases expression, increases expression	2
bisphenol S	increases expression, affects cotreatment, decreases expression	2
Cadmium	increases abundance, increases palmitoylation, decreases expression, decreases reaction	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Cadmium Chloride	increases abundance, increases palmitoylation, decreases expression, decreases reaction	2
Particulate Matter	increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
TAK-243	decreases sumoylation	1
dicrotophos	increases expression	1
geldanamycin	increases expression	1
testosterone enanthate	affects expression	1
bisphenol A	decreases expression	1
sodium arsenate	decreases expression	1
quercitrin	increases expression	1
butyraldehyde	decreases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
coumarin	affects phosphorylation	1
beta-methylcholine	affects expression	1
2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine	increases expression	1
di-n-butylphosphoric acid	affects expression	1
chloropicrin	affects expression	1
nutlin 3	affects cotreatment, increases secretion	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5697183	Binding	Inhibition of SRRM2 (unknown origin) assessed as fold change at 10 uM incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — Nature

Clinical trials (associated diseases)

202 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice