SRRM1

Summary

SRRM1 (serine and arginine repetitive matrix 1, HGNC:16638) is a protein-coding gene on chromosome 1p36.11, encoding Serine/arginine repetitive matrix protein 1 (Q8IYB3). Part of pre- and post-splicing multiprotein mRNP complexes. It is a common-essential gene (DepMap: required in 94.5% of cancer cell lines).

Enables RNA binding activity. Predicted to be involved in regulation of mRNA splicing, via spliceosome. Located in nuclear speck. Part of catalytic step 2 spliceosome. Biomarker of gestational diabetes.

Source: NCBI Gene 10250 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 129 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 94.5% of screened cell lines (common-essential)
• MANE Select transcript: NM_005839

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16638
Approved symbol	SRRM1
Name	serine and arginine repetitive matrix 1
Location	1p36.11
Locus type	gene with protein product
Status	Approved
Aliases	SRM160, POP101, MGC39488
Ensembl gene	ENSG00000133226
Ensembl biotype	protein_coding
OMIM	605975
Entrez	10250

Gene structure

Transcript identifiers

Ensembl transcripts: 63 — 45 protein_coding, 12 protein_coding_CDS_not_defined, 5 retained_intron, 1 nonsense_mediated_decay

ENST00000323848, ENST00000374389, ENST00000461768, ENST00000462710, ENST00000466910, ENST00000468822, ENST00000470243, ENST00000471693, ENST00000474843, ENST00000478890, ENST00000479034, ENST00000485441, ENST00000485541, ENST00000488317, ENST00000489130, ENST00000490543, ENST00000494934, ENST00000495561, ENST00000496882, ENST00000593639, ENST00000596378, ENST00000600523, ENST00000705662, ENST00000705663, ENST00000705681, ENST00000705682, ENST00000874368, ENST00000874369, ENST00000874370, ENST00000874371, ENST00000874372, ENST00000874373, ENST00000874374, ENST00000874375, ENST00000874376, ENST00000874377, ENST00000874378, ENST00000874379, ENST00000928562, ENST00000928563, ENST00000928564, ENST00000928565, ENST00000928566, ENST00000928567, ENST00000928568, ENST00000928569, ENST00000928570, ENST00000928571, ENST00000928572, ENST00000928573, ENST00000928574, ENST00000928575, ENST00000928576, ENST00000928577, ENST00000928578, ENST00000928579, ENST00000928580, ENST00000928581, ENST00000928582, ENST00000928583, ENST00000928584, ENST00000955599, ENST00000955600

RefSeq mRNA: 35 — MANE Select: NM_005839 NM_001303448, NM_001303449, NM_001366565, NM_001366566, NM_001366567, NM_001366568, NM_001366569, NM_001366570, NM_001366571, NM_001366572, NM_001366573, NM_001366575, NM_001366576, NM_001366577, NM_001366578, NM_001366581, NM_001366582, NM_001366584, NM_001366585, NM_001366586, NM_001366587, NM_001366588, NM_001366589, NM_001366590, NM_001366591, NM_001366592, NM_001366593, NM_001366594, NM_001366595, NM_001366596, NM_001366597, NM_001366598, NM_001366599, NM_001366600, NM_005839

CCDS: CCDS255, CCDS90883, CCDS90884, CCDS90885, CCDS90886

Canonical transcript exons

ENST00000323848 — 17 exons

Exon	Start	End
ENSE00003458578	24666815	24666925
ENSE00003508522	24670120	24670315
ENSE00003523774	24669123	24669587
ENSE00003534528	24648859	24649029
ENSE00003571641	24654855	24655129
ENSE00003584649	24652434	24652628
ENSE00003599546	24646667	24646789
ENSE00003603338	24660719	24660799
ENSE00003623707	24652913	24653032
ENSE00003637537	24645984	24646073
ENSE00003644779	24649971	24650086
ENSE00003650595	24662660	24662804
ENSE00003655059	24661310	24661396
ENSE00003670653	24651409	24651612
ENSE00003727326	24671386	24671595
ENSE00003993951	24672182	24673281
ENSE00003993990	24643302	24643347

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 99.60.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 59.2520 / max 1519.6763, expressed in 1818 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
1419	57.7428	1818
1421	0.9080	531
1420	0.4803	246
1418	0.1081	36
1422	0.0129	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus epididymis	UBERON:0004359	99.60	gold quality
sural nerve	UBERON:0015488	99.11	gold quality
caput epididymis	UBERON:0004358	98.91	gold quality
right uterine tube	UBERON:0001302	98.82	gold quality
left ovary	UBERON:0002119	98.59	gold quality
buccal mucosa cell	CL:0002336	98.46	gold quality
right ovary	UBERON:0002118	98.35	gold quality
tibial nerve	UBERON:0001323	98.26	gold quality
body of uterus	UBERON:0009853	98.25	gold quality
cauda epididymis	UBERON:0004360	98.19	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.15	gold quality
endocervix	UBERON:0000458	98.10	gold quality
cerebellar hemisphere	UBERON:0002245	97.99	gold quality
cerebellar cortex	UBERON:0002129	97.96	gold quality
seminal vesicle	UBERON:0000998	97.73	gold quality
cerebellum	UBERON:0002037	97.66	gold quality
skin of leg	UBERON:0001511	97.56	gold quality
ovary	UBERON:0000992	97.55	gold quality
left uterine tube	UBERON:0001303	97.52	gold quality
corpus callosum	UBERON:0002336	97.50	gold quality
colonic epithelium	UBERON:0000397	97.46	gold quality
skin of abdomen	UBERON:0001416	97.43	gold quality
calcaneal tendon	UBERON:0003701	97.43	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.40	gold quality
ectocervix	UBERON:0012249	97.30	gold quality
right lung	UBERON:0002167	97.21	gold quality
vagina	UBERON:0000996	97.19	gold quality
mucosa of stomach	UBERON:0001199	97.19	gold quality
zone of skin	UBERON:0000014	97.18	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.17	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-6379	no	886.76
E-CURD-10	no	772.64
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

45 targeting SRRM1, 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-3613-3P	100.00	76.36	7965
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-4470	99.66	69.35	1767
HSA-MIR-106A-3P	99.53	67.58	995
HSA-MIR-32-3P	99.36	68.20	2517
HSA-MIR-4652-3P	99.33	70.02	2742
HSA-MIR-664A-3P	99.22	71.08	2696
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-3688-5P	99.12	69.67	1091
HSA-MIR-760	98.81	66.65	1392
HSA-MIR-4297	98.77	66.95	2013
HSA-MIR-4317	98.49	67.09	987
HSA-MIR-4766-3P	98.48	67.94	1347
HSA-MIR-4536-5P	98.47	64.39	657
HSA-MIR-6771-3P	98.20	66.53	971
HSA-MIR-6870-3P	98.08	65.10	692

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 94.5% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 7)

• 1H, 13C, and 15N resonance assignments and secondary structure of the PWI domain from SRm160 was determined using reduced dimensionality NMR. (PMID:11991360)
• Proto-oncoprotein TLS/FUS is associated to the nuclear matrix and complexed with splicing factors PTB, SRm160, and SR proteins and plays a role in spliceosome assembly (PMID:12581738)
• two contiguous sequences that independently target SRm160 to nuclear matrix sites at splicing speckled domains: amino acids 300-350 and 351-688 (PMID:12624182)
• Data show that SRm160, a splicing coactivator and component of the exon junction complex (EJC) involved in RNA export, has an adenosine triphosphate (ATP)-dependent mobility. (PMID:15024032)
• found that the majority of proteins identified in SRm160-containing complexes are associated with pre-mRNA processing. Interestingly, SRm160 is also associated with factors involved in chromatin regulation and sister chromatid cohesion (PMID:16159877)
• SRm160, a splicing coactivator, regulates CD44 alternative splicing in a Ras-dependent manner. (PMID:16354706)
• We discovered that two factors, SRRM1 and SF3B1, affect not only cis-SAGe chimeras, but also other types of chimeric RNAs in a genome-wide fashion. (PMID:30590765)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Srrm1	ENSMUSG00000028809
rattus_norvegicus	Srrm1	ENSRNOG00000018194
drosophila_melanogaster	Srrm1	FBGN0036340

Protein

Protein identifiers

Serine/arginine repetitive matrix protein 1 — Q8IYB3 (reviewed: Q8IYB3)

Alternative names: SR-related nuclear matrix protein of 160 kDa, Ser/Arg-related nuclear matrix protein

All UniProt accessions (10): A0A0S2Z4W1, Q8IYB3, A0A0S2Z4Z6, A0A994J4Y3, A0A994J7H1, A0A994J7V4, A9Z1X7, M0QXG5, M0R088, M0R1E7

UniProt curated annotations — full annotation on UniProt →

Function. Part of pre- and post-splicing multiprotein mRNP complexes. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs. Involved in numerous pre-mRNA processing events. Promotes constitutive and exonic splicing enhancer (ESE)-dependent splicing activation by bridging together sequence-specific (SR family proteins, SFRS4, SFRS5 and TRA2B/SFRS10) and basal snRNP (SNRP70 and SNRPA1) factors of the spliceosome. Stimulates mRNA 3’-end cleavage independently of the formation of an exon junction complex. Binds both pre-mRNA and spliced mRNA 20-25 nt upstream of exon-exon junctions. Binds RNA and DNA with low sequence specificity and has similar preference for either double- or single-stranded nucleic acid substrates.

Subunit / interactions. Identified in the spliceosome C complex. Found in a pre-mRNA splicing complex with SFRS4, SFRS5, SNRP70, SNRPA1, SRRM1 and SRRM2. Found in a pre-mRNA exonic splicing enhancer (ESE) complex with SNRP70, SNRPA1, SRRM1 and TRA2B/SFRS10. Component of the minor spliceosome, which splices U12-type introns. Found in a mRNA splicing-dependent exon junction complex (EJC) with DEK, PRPF8, NCBP1, RBM8A, RNPS1, SRRM1 and ALYREF/THOC4. Interacts with DDX39B, CPSF1, RBM8A, RNPS1, and ALYREF/THOC4. Seems to be a compound of RNA export complexes that are released from speckles in a ATP-dependent manner.

Subcellular location. Nucleus matrix. Nucleus speckle.

Post-translational modifications. Phosphorylated on multiple serine and threonine residues by DYRK3 during the G2-to-M transition, after the nuclear-envelope breakdown. Phosphorylation by DYRK3 promotes disassembly of nuclear speckles. Citrullinated by PADI4.

Similarity. Belongs to the splicing factor SR family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8IYB3-1	1	yes
Q8IYB3-2	2

RefSeq proteins (35): NP_001290377, NP_001290378, NP_001353494, NP_001353495, NP_001353496, NP_001353497, NP_001353498, NP_001353499, NP_001353500, NP_001353501, NP_001353502, NP_001353504, NP_001353505, NP_001353506, NP_001353507, NP_001353510, NP_001353511, NP_001353513, NP_001353514, NP_001353515, NP_001353516, NP_001353517, NP_001353518, NP_001353519, NP_001353520, NP_001353521, NP_001353522, NP_001353523, NP_001353524, NP_001353525, NP_001353526, NP_001353527, NP_001353528, NP_001353529, NP_005830* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002483	PWI_dom	Domain
IPR036483	PWI_dom_sf	Homologous_superfamily
IPR052225	Ser/Arg_repetitive_matrix	Family

Pfam: PF01480

UniProt features (133 total): modified residue 77, compositionally biased region 21, cross-link 8, helix 7, region of interest 4, mutagenesis site 3, sequence conflict 3, turn 3, splice variant 2, strand 2, chain 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
7DVQ	ELECTRON MICROSCOPY	2.89
8I0R	ELECTRON MICROSCOPY	3
6FF4	ELECTRON MICROSCOPY	3.4
8I0P	ELECTRON MICROSCOPY	3.4
6FF7	ELECTRON MICROSCOPY	4.5
7ABH	ELECTRON MICROSCOPY	4.5
7ABG	ELECTRON MICROSCOPY	7.8
7ABI	ELECTRON MICROSCOPY	8
1MP1	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IYB3-F1	51.92	0.04

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 (85): 802, 872, 874, 901, 127, 231, 231, 249, 447, 459, 472, 869, 1, 7, 140, 220, 227, 234, 240, 241 …

Mutagenesis-validated functional residues (3):

Position	Phenotype
20	strongly reduces dna and rna-binding.
22	strongly reduces dna and rna-binding.
23	strongly reduces dna and rna-binding.

Function

Pathways and Gene Ontology

Reactome pathways

18 pathways

ID	Pathway
R-HSA-159236	Transport of Mature mRNA derived from an Intron-Containing Transcript
R-HSA-72163	mRNA Splicing - Major Pathway
R-HSA-72187	mRNA 3’-end processing
R-HSA-9013418	RHOBTB2 GTPase cycle
R-HSA-9013422	RHOBTB1 GTPase cycle
R-HSA-9918481	Dengue Virus-Host Interactions
R-HSA-73856	RNA Polymerase II Transcription Termination
R-HSA-162582	Signal Transduction
R-HSA-194315	Signaling by Rho GTPases
R-HSA-72172	mRNA Splicing
R-HSA-72202	Transport of Mature Transcript to Cytoplasm
R-HSA-72203	Processing of Capped Intron-Containing Pre-mRNA
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-8953854	Metabolism of RNA
R-HSA-9012999	RHO GTPase cycle
R-HSA-9706574	RHOBTB GTPase Cycle
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 209 (showing top): MORF_DNMT1, TAATAAT_MIR126, TGCGCANK_UNKNOWN, MORF_RRM1, MORF_HDAC1, MORF_UBE2N, MORF_CDK2, MORF_HDAC2, MORF_TERF1, MARTINEZ_RB1_TARGETS_UP, MORF_RAF1, OSWALD_HEMATOPOIETIC_STEM_CELL_IN_COLLAGEN_GEL_UP, GATA3_01, MORF_CCNI, REACTOME_MRNA_3_END_PROCESSING

GO Biological Process (5): RNA splicing, via transesterification reactions (GO:0000375), mRNA splicing, via spliceosome (GO:0000398), RNA splicing (GO:0008380), regulation of mRNA splicing, via spliceosome (GO:0048024), mRNA processing (GO:0006397)

GO Molecular Function (3): DNA binding (GO:0003677), RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (7): nucleus (GO:0005634), nucleoplasm (GO:0005654), spliceosomal complex (GO:0005681), cytosol (GO:0005829), nuclear matrix (GO:0016363), nuclear speck (GO:0016607), catalytic step 2 spliceosome (GO:0071013)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
Processing of Capped Intron-Containing Pre-mRNA	3
RHOBTB GTPase Cycle	2
Transport of Mature Transcript to Cytoplasm	1
mRNA Splicing	1
Dengue Virus Infection	1
RNA Polymerase II Transcription	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Metabolism of RNA	1
Gene expression (Transcription)	1
Signaling by Rho GTPases	1
RHO GTPase cycle	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
RNA processing	2
nucleic acid binding	2
nuclear lumen	2
RNA splicing	1
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
mRNA splicing, via spliceosome	1
regulation of RNA splicing	1
regulation of mRNA processing	1
mRNA metabolic process	1
binding	1
intracellular membrane-bounded organelle	1
nuclear protein-containing complex	1
ribonucleoprotein complex	1
cytoplasm	1
nuclear ribonucleoprotein granule	1
Prp19 complex	1
spliceosomal complex	1
U5 snRNP	1
catalytic complex	1

Protein interactions and networks

STRING

1812 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SRRM1	RNPS1	Q15287	994
SRRM1	SRRM2	Q9UQ35	990
SRRM1	DEK	P35659	968
SRRM1	RBM25	P49756	956
SRRM1	PNN	Q9H307	916
SRRM1	ALYREF	Q86V81	916
SRRM1	SRSF4	Q08170	858
SRRM1	UPF3A	Q9H1J1	838
SRRM1	UPF3B	Q9BZI7	821
SRRM1	MAGOH	P50606	814
SRRM1	MAGOHB	Q96A72	813
SRRM1	U2AF2	P26368	807
SRRM1	SRSF11	Q05519	799
SRRM1	DDX39B	Q13838	779
SRRM1	RBM8A	Q9Y5S9	738

IntAct

158 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:0914”(association)	0.900
CDK8	MED19	psi-mi:“MI:2364”(proximity)	0.850
SRRM1	YWHAG	psi-mi:“MI:0915”(physical association)	0.760
SRRM1	CLK2	psi-mi:“MI:0915”(physical association)	0.720
CLK2	SRRM1	psi-mi:“MI:0915”(physical association)	0.720
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
SRPK2	SRRM1	psi-mi:“MI:0915”(physical association)	0.700
SF3B1	SAP18	psi-mi:“MI:0914”(association)	0.640
P4HA3	FAM171A2	psi-mi:“MI:0914”(association)	0.640
RPL14	RRP8	psi-mi:“MI:0914”(association)	0.640
SRRM1	CLK2	psi-mi:“MI:0915”(physical association)	0.560
SRRM4	SRRM1	psi-mi:“MI:0915”(physical association)	0.560
YWHAG	SHTN1	psi-mi:“MI:0914”(association)	0.560
N	RBM47	psi-mi:“MI:0914”(association)	0.530
H1-6	ZNF724	psi-mi:“MI:0914”(association)	0.530
RBM34	NVL	psi-mi:“MI:0914”(association)	0.530
SRPK2	RRP9	psi-mi:“MI:0914”(association)	0.530
ZC3H18	AQR	psi-mi:“MI:0914”(association)	0.530
PDGFB	DKC1	psi-mi:“MI:0914”(association)	0.530

BioGRID (473): SRRM1 (Two-hybrid), SRRM1 (Affinity Capture-MS), SRRM1 (Affinity Capture-MS), SRRM1 (Affinity Capture-MS), SRRM1 (Affinity Capture-MS), SRRM1 (Affinity Capture-MS), SRRM1 (Affinity Capture-MS), SRRM1 (Affinity Capture-MS), SRRM1 (Affinity Capture-MS), SRRM1 (Affinity Capture-MS), DHX15 (Co-fractionation), GTF2E1 (Co-fractionation), NOLC1 (Co-fractionation), NUMA1 (Co-fractionation), RANBP2 (Co-fractionation)

ESM2 similar proteins: A2RVS6, A6QR16, O02008, O22315, O75494, P19018, P26686, P30352, P62995, P62996, P62997, Q01130, Q06A98, Q08170, Q10021, Q13595, Q15287, Q16629, Q1PDV2, Q28E41, Q3KPW1, Q3MHR5, Q3T106, Q3ZBT6, Q4R5N1, Q52KI8, Q5NVM8, Q5R1W5, Q5R5Q2, Q5XG24, Q5ZMJ9, Q62093, Q6AYK1, Q6PDU1, Q6PFR5, Q6PG31, Q84TH4, Q8BL97, Q8IYB3, Q8RWY7

Diamond homologs: Q52KI8, Q5R5Q2, Q5ZMJ9, Q8IYB3, Q9USH5

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 171 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
Transport of Mature Transcript to Cytoplasm	10	32.8×	1e-11
RNA Polymerase II Transcription Termination	13	24.6×	2e-13
mRNA 3’-end processing	14	23.8×	4e-14
mRNA Splicing	21	19.9×	2e-19
Transport of Mature mRNA derived from an Intron-Containing Transcript	14	18.4×	1e-12
Processing of Capped Intron-Containing Pre-mRNA	22	15.6×	3e-18
mRNA Splicing - Major Pathway	29	13.7×	2e-22
mRNA Polyadenylation	18	13.6×	7e-14

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of mRNA splicing, via spliceosome	7	35.8×	1e-07
regulation of alternative mRNA splicing, via spliceosome	13	21.2×	1e-11
mRNA export from nucleus	8	15.8×	5e-06
nuclear-transcribed mRNA catabolic process, nonsense-mediated decay	5	15.6×	2e-03
mRNA splicing, via spliceosome	22	13.4×	8e-16
cytoplasmic translation	10	12.3×	1e-06
mRNA stabilization	5	12.2×	4e-03
RNA splicing	19	11.2×	3e-12

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	110
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3367 predictions. Top by Δscore:

Variant	Effect	Δscore
1:24643346:GC:G	donor_gain	1.0000
1:24643348:G:GG	donor_gain	1.0000
1:24645979:T:TA	acceptor_gain	1.0000
1:24645981:CA:C	acceptor_loss	1.0000
1:24645982:A:AG	acceptor_gain	1.0000
1:24645982:AG:A	acceptor_gain	1.0000
1:24645982:AGG:A	acceptor_gain	1.0000
1:24645983:G:A	acceptor_loss	1.0000
1:24645983:G:GA	acceptor_gain	1.0000
1:24645983:GG:G	acceptor_gain	1.0000
1:24645983:GGG:G	acceptor_gain	1.0000
1:24645983:GGGA:G	acceptor_gain	1.0000
1:24645983:GGGAA:G	acceptor_gain	1.0000
1:24646072:AGGT:A	donor_loss	1.0000
1:24646662:A:AG	acceptor_gain	1.0000
1:24646663:T:G	acceptor_gain	1.0000
1:24646665:A:G	acceptor_loss	1.0000
1:24646781:G:GT	donor_gain	1.0000
1:24646785:TGAAG:T	donor_loss	1.0000
1:24646786:GAAGG:G	donor_loss	1.0000
1:24646787:AAG:A	donor_gain	1.0000
1:24646787:AAGGT:A	donor_loss	1.0000
1:24646788:AGGTA:A	donor_loss	1.0000
1:24646789:GGTA:G	donor_loss	1.0000
1:24646790:G:GA	donor_loss	1.0000
1:24646791:T:G	donor_loss	1.0000
1:24648844:C:A	acceptor_gain	1.0000
1:24648846:T:TA	acceptor_gain	1.0000
1:24648854:T:TA	acceptor_gain	1.0000
1:24648857:A:AG	acceptor_gain	1.0000

AlphaMissense

5692 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:24643336:G:A	G4R	1.000
1:24643336:G:C	G4R	1.000
1:24643337:G:A	G4E	1.000
1:24643339:T:C	F5L	1.000
1:24643340:T:C	F5S	1.000
1:24643340:T:G	F5C	1.000
1:24643341:T:A	F5L	1.000
1:24643341:T:G	F5L	1.000
1:24643342:T:A	F6I	1.000
1:24643342:T:C	F6L	1.000
1:24643342:T:G	F6V	1.000
1:24643343:T:C	F6S	1.000
1:24643343:T:G	F6C	1.000
1:24643344:C:A	F6L	1.000
1:24643344:C:G	F6L	1.000
1:24645984:G:A	G8R	1.000
1:24645984:G:C	G8R	1.000
1:24645985:G:A	G8E	1.000
1:24645985:G:T	G8V	1.000
1:24645988:C:T	T9I	1.000
1:24645990:A:C	S10R	1.000
1:24645992:T:A	S10R	1.000
1:24645992:T:G	S10R	1.000
1:24646000:A:C	Q13P	1.000
1:24646001:G:C	Q13H	1.000
1:24646001:G:T	Q13H	1.000
1:24646002:G:C	D14H	1.000
1:24646002:G:T	D14Y	1.000
1:24646003:A:C	D14A	1.000
1:24646003:A:G	D14G	1.000

dbSNP variants (sampled 300 via entrez): RS1000039548 (1:24641889 T>A,C), RS1000136852 (1:24659836 A>G), RS1000168462 (1:24645775 T>C), RS1000200078 (1:24645470 T>TAA), RS1000222346 (1:24650941 A>T), RS1000278775 (1:24642346 G>A,C), RS1000330779 (1:24642135 G>A), RS1000445633 (1:24658042 T>C), RS1000556107 (1:24641653 AAC>A), RS1000670113 (1:24642980 C>G,T), RS1000682330 (1:24650624 A>G), RS1000745495 (1:24652103 C>G), RS1000836478 (1:24656538 A>T), RS1000861322 (1:24665755 A>G), RS1001066434 (1:24671229 A>G)

Disease associations

OMIM: gene MIM:605975 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): neurodevelopmental disorder (MONDO:0700092)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST005168_2	Systolic blood pressure	1.000000e-06
GCST006661_182	Male-pattern baldness	1.000000e-10
GCST010241_429	Apolipoprotein A1 levels	4.000000e-12
GCST010242_376	HDL cholesterol levels	3.000000e-10
GCST010988_524	Adult body size	3.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0006335	systolic blood pressure
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement

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): CHEMBL5725075 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	3
Cadmium	decreases expression, increases abundance	2
Cadmium Chloride	increases expression, decreases expression, increases abundance, decreases methylation	2
GSK-J4	increases expression	1
FR900359	increases phosphorylation	1
TAK-243	decreases sumoylation	1
dicrotophos	increases expression	1
methylmercuric chloride	increases expression	1
alpha-pinene	affects cotreatment, decreases expression, increases oxidation, increases abundance	1
uranyl acetate	affects expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
bisphenol A	decreases expression	1
sodium arsenate	decreases expression	1
pyrogallol 1,3-dimethyl ether	increases expression, affects cotreatment, affects localization	1
beta-lapachone	increases expression	1
methylparaben	increases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
coumarin	affects phosphorylation	1
methacrylaldehyde	decreases expression, increases oxidation, increases abundance, affects cotreatment	1
epigallocatechin gallate	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
bisphenol S	increases expression	1
bisphenol AF	increases expression	1
Vorinostat	decreases expression	1
Acrolein	affects cotreatment, decreases expression, increases oxidation, increases abundance	1
Air Pollutants	affects cotreatment, decreases expression, increases abundance, increases oxidation	1
Arsenic	increases abundance, increases expression	1
Benzo(a)pyrene	increases methylation	1
Caffeine	affects phosphorylation	1
Cisplatin	decreases expression	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5697738	Binding	Inhibition of SRRM1 (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