NSRP1

Summary

NSRP1 (nuclear speckle splicing regulatory protein 1, HGNC:25305) is a protein-coding gene on chromosome 17q11.2, encoding Nuclear speckle splicing regulatory protein 1 (Q9H0G5). RNA-binding protein that mediates pre-mRNA alternative splicing regulation. It is a selective cancer dependency (DepMap: 26.4% of cell lines).

Enables mRNA binding activity. Involved in developmental process and regulation of alternative mRNA splicing, via spliceosome. Located in nuclear speck. Part of ribonucleoprotein complex.

Source: NCBI Gene 84081 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder with spasticity, seizures, and brain abnormalities (Strong, GenCC)
• GWAS associations: 3
• Clinical variants (ClinVar): 79 total — 3 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 36
• Cancer dependency (DepMap): dependent in 26.4% of screened cell lines
• MANE Select transcript: NM_032141

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25305
Approved symbol	NSRP1
Name	nuclear speckle splicing regulatory protein 1
Location	17q11.2
Locus type	gene with protein product
Status	Approved
Aliases	DKFZP434K1421, NSrp70
Ensembl gene	ENSG00000126653
Ensembl biotype	protein_coding
OMIM	616173
Entrez	84081

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 9 protein_coding, 5 nonsense_mediated_decay, 4 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000247026, ENST00000394826, ENST00000467446, ENST00000475652, ENST00000479218, ENST00000540900, ENST00000577289, ENST00000580103, ENST00000581048, ENST00000583301, ENST00000584154, ENST00000584317, ENST00000584423, ENST00000585881, ENST00000588614, ENST00000589608, ENST00000612959, ENST00000870657, ENST00000930609

RefSeq mRNA: 2 — MANE Select: NM_032141 NM_001261467, NM_032141

CCDS: CCDS11255, CCDS74025

Canonical transcript exons

ENST00000247026 — 7 exons

Exon	Start	End
ENSE00001906322	30184615	30186475
ENSE00003479074	30172542	30172598
ENSE00003519306	30178071	30178199
ENSE00003555566	30118080	30118173
ENSE00003562538	30180908	30181016
ENSE00003659893	30179090	30179297
ENSE00003843705	30116816	30116863

Expression profiles

Bgee: expression breadth ubiquitous, 260 present calls, max score 98.53.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 41.2744 / max 2985.0784, expressed in 1817 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
160123	39.8320	1817
160122	0.8140	421
160124	0.6283	302

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	98.53	gold quality
tibia	UBERON:0000979	97.09	gold quality
parietal pleura	UBERON:0002400	96.25	gold quality
visceral pleura	UBERON:0002401	96.17	gold quality
calcaneal tendon	UBERON:0003701	95.77	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	94.60	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	94.29	gold quality
kidney epithelium	UBERON:0004819	94.23	gold quality
cartilage tissue	UBERON:0002418	93.86	gold quality
spinal cord	UBERON:0002240	93.79	gold quality
left ventricle myocardium	UBERON:0006566	93.57	gold quality
colonic epithelium	UBERON:0000397	93.56	gold quality
cardiac muscle of right atrium	UBERON:0003379	93.32	silver quality
popliteal artery	UBERON:0002250	93.29	gold quality
tibial artery	UBERON:0007610	93.29	gold quality
oral cavity	UBERON:0000167	93.28	gold quality
descending thoracic aorta	UBERON:0002345	93.26	gold quality
islet of Langerhans	UBERON:0000006	93.21	gold quality
artery	UBERON:0001637	93.09	gold quality
upper arm skin	UBERON:0004263	92.97	gold quality
mucosa of stomach	UBERON:0001199	92.79	gold quality
saphenous vein	UBERON:0007318	92.72	gold quality
layer of synovial tissue	UBERON:0007616	92.72	gold quality
aorta	UBERON:0000947	92.68	gold quality
myocardium	UBERON:0002349	92.60	gold quality
palpebral conjunctiva	UBERON:0001812	92.21	gold quality
substantia nigra	UBERON:0002038	92.19	gold quality
right coronary artery	UBERON:0001625	92.18	gold quality
seminal vesicle	UBERON:0000998	92.17	gold quality
tendon	UBERON:0000043	92.11	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.60

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

40 targeting NSRP1, 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-5011-5P	100.00	83.46	5820
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-1303	99.65	69.77	1662
HSA-MIR-582-5P	99.47	70.79	2635
HSA-MIR-516A-3P	99.46	67.96	1378
HSA-MIR-516B-3P	99.46	67.96	1378
HSA-MIR-7162-5P	99.46	68.08	1368
HSA-MIR-4652-3P	99.33	70.02	2742
HSA-MIR-548L	99.06	70.90	2560
HSA-MIR-7702	99.06	65.95	698
HSA-MIR-7151-3P	99.04	69.72	2370
HSA-MIR-670-3P	99.03	68.88	2404
HSA-MIR-3926	98.95	69.26	1438
HSA-MIR-1911-5P	98.92	67.53	325
HSA-MIR-4424	98.91	70.33	1145
HSA-MIR-3190-5P	98.87	64.89	1345
HSA-MIR-367-5P	98.84	67.18	902
HSA-MIR-3074-5P	98.82	66.56	1414
HSA-MIR-5197-3P	98.71	67.05	1905
HSA-MIR-603	98.58	68.28	1603

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 26.4% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 5)

• We showed that NSRP70 is a novel lymphoblastic acute leukemia surrogate marker (PMID:25176346)
• Coiled coil domain-containing 55 gene may be involved in a functional bridging between the CNR1 activation and the disrupted in schizophrenia 1/Ran binding protein 9-associated pathways. (PMID:26475744)
• NSrp70 acts as a new molecular counterpart for alternative splicing of target RNA, counteracting SRSF1 and SRSF2 splicing activity. (PMID:26797131)
• Biallelic loss-of-function variants in the splicing regulator NSRP1 cause a severe neurodevelopmental disorder with spastic cerebral palsy and epilepsy. (PMID:34385670)
• NSrp70 suppresses metastasis in triple-negative breast cancer by modulating Numb/TbetaR1/EMT axis. (PMID:35568738)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	nsrp1	ENSDARG00000015221
mus_musculus	Nsrp1	ENSMUSG00000037958
rattus_norvegicus	Nsrp1	ENSRNOG00000062400
drosophila_melanogaster	CG15747	FBGN0030474
caenorhabditis_elegans		WBGENE00007627

Paralogs (1): EFCAB5 (ENSG00000176927)

Protein

Protein identifiers

Nuclear speckle splicing regulatory protein 1 — Q9H0G5 (reviewed: Q9H0G5)

Alternative names: Coiled-coil domain-containing protein 55, Nuclear speckle-related protein 70

All UniProt accessions (11): Q9H0G5, A0A024QZ33, H7BYM1, J3KT62, J3QLV5, J3QRI6, J3QS82, K7EK40, K7EMD8, K7EQJ6, K7ERM9

UniProt curated annotations — full annotation on UniProt →

Function. RNA-binding protein that mediates pre-mRNA alternative splicing regulation. Through CCDC118 regulation, may promote pre-adipocyte differentiation.

Subunit / interactions. Interacts (via C-terminus) with SRSF1/ASF. Interacts (via C-terminus) with SRSF2/SC35.

Subcellular location. Nucleus. Nucleus speckle.

Tissue specificity. Expressed in dendritic cells, T-cells, B-cells and natural killer cells. Expressed in secondary lymphoid organs such as spleen and mesenteric, axillary and brachial lymph nodes.

Disease relevance. Neurodevelopmental disorder with spasticity, seizures, and brain abnormalities (NEDSSBA) [MIM:620001] An autosomal recessive disorder characterized by developmental delay apparent in infancy, impaired intellectual development with poor or absent speech, epilepsy, variable microcephaly, hypotonia, and spastic cerebral palsy. Brain abnormalities include simplified gyral pattern, defects of the operculum, and vermian hypoplasia. Death in early childhood may occur. The disease is caused by variants affecting the gene represented in this entry.

Induction. Up-regulated in motile T-cells.

Similarity. Belongs to the NSRP1 family.

RefSeq proteins (2): NP_001248396, NP_115517* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR018612	NSRP1_N	Domain
IPR042816	Nsrp1	Family
IPR046850	NRP1_C	Domain

Pfam: PF09745, PF20427

UniProt features (29 total): compositionally biased region 7, modified residue 7, region of interest 4, cross-link 3, sequence variant 2, mutagenesis site 2, coiled-coil region 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H0G5-F1	62.95	0.09

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 (10): 27, 33, 248, 254, 255, 275, 457, 199, 210, 281

Mutagenesis-validated functional residues (2):

Position	Phenotype
536	loss of nuclear localization and alternative splicing activity.
537	loss of nuclear localization and alternative splicing activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-72163	mRNA Splicing - Major Pathway

MSigDB gene sets: 185 (showing top): GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_ALTERNATIVE_MRNA_SPLICING_VIA_SPLICEOSOME, chr17q11, GOBP_IN_UTERO_EMBRYONIC_DEVELOPMENT, FREAC3_01, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, WTGAAAT_UNKNOWN, GOBP_RNA_SPLICING, REACTOME_MRNA_SPLICING, DOUGLAS_BMI1_TARGETS_DN, GOBP_REGULATION_OF_MRNA_SPLICING_VIA_SPLICEOSOME, GOBP_CONNECTIVE_TISSUE_DEVELOPMENT, NOUZOVA_TRETINOIN_AND_H4_ACETYLATION, GOBP_EMBRYO_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_DEVELOPMENTAL_PROCESS

GO Biological Process (6): regulation of alternative mRNA splicing, via spliceosome (GO:0000381), in utero embryonic development (GO:0001701), mRNA processing (GO:0006397), RNA splicing (GO:0008380), developmental process (GO:0032502), positive regulation of adipose tissue development (GO:1904179)

GO Molecular Function (3): RNA binding (GO:0003723), mRNA binding (GO:0003729), protein binding (GO:0005515)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), nuclear speck (GO:0016607), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
mRNA Splicing	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA processing	2
alternative mRNA splicing, via spliceosome	1
regulation of mRNA splicing, via spliceosome	1
chordate embryonic development	1
mRNA metabolic process	1
biological_process	1
positive regulation of developmental process	1
positive regulation of multicellular organismal process	1
adipose tissue development	1
regulation of adipose tissue development	1
nucleic acid binding	1
RNA binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
nuclear ribonucleoprotein granule	1
protein-containing complex	1

Protein interactions and networks

STRING

984 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NSRP1	DHX40	Q8IX18	576
NSRP1	EFCAB5	A4FU69	552
NSRP1	SRSF1	Q07955	526
NSRP1	SLC71A3P	Q5VZR4	505
NSRP1	SRSF11	Q05519	460
NSRP1	MRPS34	P82930	452
NSRP1	H3BUI4	H3BUI4	448
NSRP1	LYAR	Q9NX58	428
NSRP1	PFAS	O15067	425
NSRP1	SRSF2	Q01130	421
NSRP1	KHDRBS3	O75525	416
NSRP1	SRRM1	Q8IYB3	407
NSRP1	RNF121	Q9H920	379
NSRP1	RIPOR3	Q96MK2	376
NSRP1	COMTD1	Q86VU5	376

IntAct

79 interactions, top by confidence:

A	B	Type	Score
PAIP1	PABPC1	psi-mi:“MI:0914”(association)	0.970
CDK8	MED19	psi-mi:“MI:2364”(proximity)	0.850
RIOK1	PRMT5	psi-mi:“MI:0914”(association)	0.710
SPTLC1	SPTLC2	psi-mi:“MI:0914”(association)	0.680
SF3B1	SAP18	psi-mi:“MI:0914”(association)	0.640
SRPK2	NSRP1	psi-mi:“MI:0217”(phosphorylation reaction)	0.590
RIOK2	BYSL	psi-mi:“MI:0914”(association)	0.530
EZH1	EPOP	psi-mi:“MI:0914”(association)	0.530
CDK18	UBL4A	psi-mi:“MI:0914”(association)	0.530
NSRP1	PPIL4	psi-mi:“MI:0914”(association)	0.480
ENG	NSRP1	psi-mi:“MI:0407”(direct interaction)	0.440
	NSRP1	psi-mi:“MI:0407”(direct interaction)	0.440
SRPK1	NSRP1	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
H3C1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.410
NSRP1	CTNNBL1	psi-mi:“MI:0915”(physical association)	0.370
CHORDC1	SSR3	psi-mi:“MI:0914”(association)	0.350
MYO1C	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
Junb	RGPD3	psi-mi:“MI:0914”(association)	0.350
XRCC3	DERL1	psi-mi:“MI:0914”(association)	0.350
EMC2	TBL2	psi-mi:“MI:0914”(association)	0.350
MMGT1	DERL1	psi-mi:“MI:0914”(association)	0.350
JMJD6	U2SURP	psi-mi:“MI:0914”(association)	0.350
Vav2	CALU	psi-mi:“MI:0914”(association)	0.350
ARHGAP11A	LTF	psi-mi:“MI:0914”(association)	0.350
CCNT1	CBX4	psi-mi:“MI:0914”(association)	0.350
NDC80	SART1	psi-mi:“MI:0914”(association)	0.350
SP100	SART1	psi-mi:“MI:0914”(association)	0.350
P		psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350

BioGRID (227): NSRP1 (Affinity Capture-MS), NSRP1 (Affinity Capture-MS), NSRP1 (Affinity Capture-MS), NSRP1 (Affinity Capture-MS), NSRP1 (Affinity Capture-MS), NSRP1 (Affinity Capture-MS), NSRP1 (Affinity Capture-MS), NSRP1 (Affinity Capture-MS), NSRP1 (Affinity Capture-RNA), NSRP1 (Affinity Capture-MS), NSRP1 (Affinity Capture-MS), NSRP1 (Affinity Capture-MS), NSRP1 (Affinity Capture-MS), NSRP1 (Proximity Label-MS), NSRP1 (Affinity Capture-MS)

ESM2 similar proteins: A2AJT4, A2CG63, B0S733, F1QNX7, G3V8T1, O75376, O94988, P29536, Q02040, Q14241, Q149C2, Q15695, Q15696, Q28G87, Q2KIC0, Q4FZU3, Q4G0J3, Q4KKX4, Q4LE39, Q4R627, Q53F19, Q561R3, Q5NCR9, Q5R4U2, Q5RL73, Q5U2T3, Q5XIN3, Q5ZM19, Q60974, Q62377, Q63187, Q64707, Q6PFK1, Q6PGZ3, Q8BZR9, Q8C761, Q8CB77, Q8K2X2, Q8QG78, Q8TDR0

Diamond homologs: A8XXB0, Q09252, Q2KIC0, Q4FZU3, Q5NCR9, Q9H0G5, O14009, Q568R1

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 114 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
mRNA Splicing	14	19.0×	3e-12
Processing of Capped Intron-Containing Pre-mRNA	15	15.2×	6e-12
mRNA Polyadenylation	14	15.2×	3e-11
mRNA Splicing - Major Pathway	22	14.8×	1e-17
mRNA 3’-end processing	5	12.2×	3e-03
CHD1 and CHD2 subfamily	7	9.4×	6e-04
Transport of Mature mRNA derived from an Intron-Containing Transcript	5	9.4×	9e-03
Metabolism of RNA	18	9.3×	4e-11

GO biological processes:

GO term	Partners	Fold	FDR
U2-type prespliceosome assembly	6	36.4×	3e-06
mRNA splicing, via spliceosome	20	17.8×	6e-17
ribosomal small subunit biogenesis	5	11.1×	6e-03
RNA splicing	12	10.3×	6e-07
mRNA processing	11	8.4×	1e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	2
Uncertain significance	61
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
1047905	NM_032141.4(NSRP1):c.1359_1362del (p.Glu455fs)	Pathogenic
1047906	NM_032141.4(NSRP1):c.1272dup (p.Lys425fs)	Pathogenic
1687281	NM_032141.4(NSRP1):c.1324del (p.Glu441_Val442insTer)	Pathogenic
1706591	NM_032141.4(NSRP1):c.24T>G (p.Tyr8Ter)	Likely pathogenic
3775177	NM_032141.4(NSRP1):c.1048_1054dup (p.Arg352delinsLysSerTer)	Likely pathogenic

SpliceAI

1798 predictions. Top by Δscore:

Variant	Effect	Δscore
17:30116836:G:GT	donor_gain	1.0000
17:30116861:GCA:G	donor_gain	1.0000
17:30116864:G:GG	donor_gain	1.0000
17:30116876:G:GT	donor_gain	1.0000
17:30118063:A:AG	acceptor_gain	1.0000
17:30118064:A:G	acceptor_gain	1.0000
17:30172536:TTACA:T	acceptor_loss	1.0000
17:30172537:TACA:T	acceptor_loss	1.0000
17:30172538:ACAGA:A	acceptor_loss	1.0000
17:30172539:CAGA:C	acceptor_loss	1.0000
17:30172540:A:AG	acceptor_gain	1.0000
17:30172540:A:AT	acceptor_loss	1.0000
17:30172541:G:GG	acceptor_gain	1.0000
17:30172541:GAC:G	acceptor_gain	1.0000
17:30172541:GACCT:G	acceptor_gain	1.0000
17:30178068:A:AG	acceptor_gain	1.0000
17:30178068:AAGA:A	acceptor_loss	1.0000
17:30178069:A:G	acceptor_gain	1.0000
17:30178070:G:GA	acceptor_gain	1.0000
17:30178070:GAC:G	acceptor_gain	1.0000
17:30178070:GACC:G	acceptor_gain	1.0000
17:30178070:GACCA:G	acceptor_gain	1.0000
17:30178158:G:GT	donor_gain	1.0000
17:30178162:A:T	donor_gain	1.0000
17:30178195:GAAAG:G	donor_gain	1.0000
17:30178197:AAGG:A	donor_loss	1.0000
17:30178198:AGG:A	donor_loss	1.0000
17:30178200:G:GA	donor_loss	1.0000
17:30178200:GTTT:G	donor_gain	1.0000
17:30178204:G:GG	donor_gain	1.0000

AlphaMissense

3782 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:30178122:T:C	Y75H	0.999
17:30179131:A:C	R114S	0.999
17:30179131:A:T	R114S	0.999
17:30179198:T:C	F137L	0.999
17:30179200:T:A	F137L	0.999
17:30179200:T:G	F137L	0.999
17:30179216:T:C	F143L	0.999
17:30179218:T:A	F143L	0.999
17:30179218:T:G	F143L	0.999
17:30178092:G:C	A65P	0.998
17:30178123:A:G	Y75C	0.998
17:30179109:T:C	L107S	0.998
17:30179117:G:C	A110P	0.998
17:30179178:G:C	R130P	0.998
17:30179217:T:G	F143C	0.998
17:30180947:T:C	F183S	0.998
17:30178096:T:C	L66P	0.997
17:30178114:T:A	V72E	0.997
17:30178125:G:C	D76H	0.997
17:30178126:A:C	D76A	0.997
17:30178126:A:T	D76V	0.997
17:30179096:T:C	Y103H	0.997
17:30179097:A:G	Y103C	0.997
17:30179130:G:C	R114T	0.997
17:30179231:T:G	Y148D	0.997
17:30179236:G:C	K149N	0.997
17:30179236:G:T	K149N	0.997
17:30179244:T:C	L152P	0.997
17:30185622:G:C	R542T	0.997
17:30178093:C:A	A65D	0.996

dbSNP variants (sampled 300 via entrez): RS1000042731 (17:30183669 A>G), RS1000152164 (17:30124543 A>G), RS1000162723 (17:30166933 C>T), RS1000183706 (17:30124170 G>A,T), RS1000221662 (17:30116946 C>G,T), RS1000225099 (17:30159004 A>G), RS1000256420 (17:30180592 A>G,T), RS1000261897 (17:30160136 C>T), RS1000262772 (17:30118062 C>A,G), RS1000332638 (17:30160389 G>T), RS1000338227 (17:30172311 A>G,T), RS1000435510 (17:30123742 TAA>T), RS1000441235 (17:30153484 G>A), RS1000469545 (17:30130755 A>G), RS1000550544 (17:30140928 C>T)

Disease associations

OMIM: gene MIM:616173 | disease phenotypes: MIM:620001

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder with spasticity, seizures, and brain abnormalities	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
neurodevelopmental disorder with spasticity, seizures, and brain abnormalities	Moderate	AR

Mondo (2): microcephaly (MONDO:0001149), neurodevelopmental disorder with spasticity, seizures, and brain abnormalities (MONDO:0859275)

Orphanet (0):

HPO phenotypes

36 total (30 of 36 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000218	High palate
HP:0000252	Microcephaly
HP:0000303	Mandibular prognathia
HP:0000316	Hypertelorism
HP:0000322	Short philtrum
HP:0000343	Long philtrum
HP:0000348	High forehead
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000411	Protruding ear
HP:0000463	Anteverted nares
HP:0000494	Downslanted palpebral fissures
HP:0001250	Seizure
HP:0001263	Global developmental delay
HP:0001320	Cerebellar vermis hypoplasia
HP:0001344	Absent speech
HP:0001347	Hyperreflexia
HP:0001371	Flexion contracture
HP:0001508	Failure to thrive
HP:0002015	Dysphagia
HP:0002365	Hypoplasia of the brainstem
HP:0003593	Infantile onset
HP:0003623	Neonatal onset
HP:0005280	Depressed nasal bridge
HP:0005487	Prominent metopic ridge
HP:0006989	Dysplastic corpus callosum
HP:0008070	Sparse hair
HP:0008936	Axial hypotonia
HP:0009879	Simplified gyral pattern

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002650_7	Coffee consumption (cups per day)	3.000000e-08
GCST003872_16	QRS complex (12-leadsum)	6.000000e-09
GCST010703_115	Brain morphology (MOSTest)	1.000000e-28

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004330	coffee consumption
EFO:0006782	cups of coffee per day measurement
EFO:0005054	QRS complex
EFO:0007742	QRS amplitude
EFO:0004346	neuroimaging measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs6505162	MIR3184, MIR423, NSRP1		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cadmium	decreases expression, increases abundance, increases expression	2
Valproic Acid	affects expression, increases expression	2
Cyclosporine	increases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
dicrotophos	decreases expression	1
coumarin	affects phosphorylation	1
methacrylaldehyde	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
cylindrospermopsin	increases expression	1
K 7174	increases expression	1
nutlin 3	affects cotreatment, increases secretion	1
abrine	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Acrolein	affects cotreatment, decreases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Benzo(a)pyrene	increases methylation	1
Caffeine	affects phosphorylation	1
Cisplatin	affects cotreatment, decreases expression	1
Clorgyline	increases expression	1
Dactinomycin	affects cotreatment, increases secretion	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ozone	affects cotreatment, decreases expression	1
Phenobarbital	affects expression	1
Phthalic Acids	increases methylation	1
Plant Extracts	affects cotreatment, increases expression	1
Quercetin	increases expression	1
Ribonucleotides	affects binding	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05518188	PHASE1/PHASE2	RECRUITING	Melpida: Recombinant Adeno-associated Virus (serotype 9) Encoding a Codon Optimized Human AP4M1 Transgene (hAP4M1opt)
NCT00001639	Not specified	COMPLETED	Evaluation of Patients With Unresolved Chromosome Abnormalities
NCT01151462	Not specified	WITHDRAWN	Postnatal HCMV Infection in Very Preterm Infants. Implications, Morbidity, Growth and Neurodevelopmental Outcomes.
NCT01565005	Not specified	COMPLETED	Microcephaly Genetic Deficiency in Neural Progenitors
NCT02510170	Not specified	COMPLETED	Fetal and Maternal Head Circumference During Pregnancy in Israeli Population
NCT02741882	Not specified	COMPLETED	Zika and Microcephaly: Case-control Study
NCT02943304	Not specified	COMPLETED	Neurodevelopment Outcome of Newborns Exposed to Zika Virus (ZIKV) in Utero
NCT03255369	Not specified	UNKNOWN	Vertical Exposure to Zika Virus and Its Consequences for Child Neurodevelopment (ZIKVIRUSIFF)
NCT03325946	Not specified	RECRUITING	The FBRI VTC Neuromotor Research Clinic
NCT03330600	Not specified	COMPLETED	Efficacy of Aquatic Physiotherapy in Children With Microcephaly by Zika Virus Congenital Syndrome
NCT03548779	Not specified	COMPLETED	North Carolina Genomic Evaluation by Next-generation Exome Sequencing, 2
NCT03651687	Not specified	COMPLETED	Guangzhou Surveillance and Clinical Study in Microcephaly (GSCSM)
NCT03922594	Not specified	TERMINATED	Surveillance of Zika-related Microcephaly in Sub-Saharan Africa and Asia
NCT04816175	Not specified	COMPLETED	Intensive Therapy for Children With Microcephaly, Hyperkinetic Movements, or Global Developmental Delay
NCT05322980	Not specified	COMPLETED	Summary of Infants Weighing 500 Grams or Less
NCT06019182	Not specified	RECRUITING	MEHMO Natural History and Biomarkers
NCT06566066	Not specified	RECRUITING	Register for Patients With Thyroid Hormone Resistance.