RSRC1

Summary

RSRC1 (arginine and serine rich coiled-coil 1, HGNC:24152) is a protein-coding gene on chromosome 3q25.32, encoding Serine/Arginine-related protein 53 (Q96IZ7). Has a role in alternative splicing and transcription regulation.

This gene encodes a member of the serine and arginine rich-related protein family. The encoded protein is involved in both constitutive and alternative mRNA splicing. This gene may be associated with schizophrenia. A pseudogene of this gene is located on chromosome 9. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 51319 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 22
• Clinical variants (ClinVar): 88 total — 7 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 18
• MANE Select transcript: NM_001271838

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24152
Approved symbol	RSRC1
Name	arginine and serine rich coiled-coil 1
Location	3q25.32
Locus type	gene with protein product
Status	Approved
Aliases	MGC12197, BM-011, SRrp53, SFRS21
Ensembl gene	ENSG00000174891
Ensembl biotype	protein_coding
OMIM	613352
Entrez	51319

Gene structure

Transcript identifiers

Ensembl transcripts: 39 — 24 protein_coding, 8 protein_coding_CDS_not_defined, 4 nonsense_mediated_decay, 3 retained_intron

ENST00000295930, ENST00000312179, ENST00000464171, ENST00000468344, ENST00000471911, ENST00000471994, ENST00000475278, ENST00000476899, ENST00000477788, ENST00000480119, ENST00000480820, ENST00000482822, ENST00000494002, ENST00000496268, ENST00000611884, ENST00000682164, ENST00000682221, ENST00000682500, ENST00000683137, ENST00000683394, ENST00000683516, ENST00000683733, ENST00000683831, ENST00000683899, ENST00000684156, ENST00000684353, ENST00000684512, ENST00000684604, ENST00000684683, ENST00000881664, ENST00000881665, ENST00000881666, ENST00000881667, ENST00000936759, ENST00000936760, ENST00000936761, ENST00000948232, ENST00000948233, ENST00000948234

RefSeq mRNA: 3 — MANE Select: NM_001271838 NM_001271834, NM_001271838, NM_016625

CCDS: CCDS3181, CCDS63822

Canonical transcript exons

ENST00000611884 — 10 exons

Exon	Start	End
ENSE00003493360	158298039	158298075
ENSE00003532335	158123866	158123991
ENSE00003587733	158537092	158537198
ENSE00003603863	158543335	158543487
ENSE00003660240	158122103	158122298
ENSE00003661098	158460935	158461003
ENSE00003714817	158110089	158110223
ENSE00003789690	158354857	158354908
ENSE00003790633	158203072	158203245
ENSE00003891495	158544183	158545730

Expression profiles

Bgee: expression breadth ubiquitous, 264 present calls, max score 98.03.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 39.6279 / max 2153.0421, expressed in 1805 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
39494	35.0126	1796
39495	1.9694	1052
39492	1.8619	637
39498	0.5395	249
39493	0.1892	95
39491	0.0552	24

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	98.03	gold quality
sural nerve	UBERON:0015488	94.41	gold quality
tendon	UBERON:0000043	94.32	gold quality
tendon of biceps brachii	UBERON:0008188	91.76	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.80	gold quality
colonic epithelium	UBERON:0000397	90.47	gold quality
saphenous vein	UBERON:0007318	90.20	gold quality
adrenal tissue	UBERON:0018303	88.89	gold quality
popliteal artery	UBERON:0002250	88.88	gold quality
tibial artery	UBERON:0007610	88.86	gold quality
islet of Langerhans	UBERON:0000006	88.38	gold quality
corpus callosum	UBERON:0002336	88.32	gold quality
cerebellar cortex	UBERON:0002129	87.23	gold quality
cerebellar hemisphere	UBERON:0002245	87.21	gold quality
prefrontal cortex	UBERON:0000451	87.11	gold quality
secondary oocyte	CL:0000655	86.90	gold quality
aorta	UBERON:0000947	86.61	gold quality
lateral nuclear group of thalamus	UBERON:0002736	86.42	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	86.34	gold quality
cerebellum	UBERON:0002037	86.06	gold quality
monocyte	CL:0000576	85.99	gold quality
anterior cingulate cortex	UBERON:0009835	85.76	gold quality
mononuclear cell	CL:0000842	85.67	gold quality
cingulate cortex	UBERON:0003027	85.63	gold quality
rectum	UBERON:0001052	85.61	gold quality
right hemisphere of cerebellum	UBERON:0014890	85.61	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.59	gold quality
medial globus pallidus	UBERON:0002477	85.55	gold quality
oocyte	CL:0000023	85.37	gold quality
leukocyte	CL:0000738	85.29	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-6386	no	209.05
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

45 targeting RSRC1, 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-3163	100.00	77.23	8605
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-302B-5P	99.50	69.49	1857

Literature-anchored findings (GeneRIF, showing 6)

• This study use Functional MRI and Genome Wide Association Analysis indentic novel gene(RSRC1) associated with schizophrenia. (PMID:19065146)
• Data indicate that arginine/serine-rich coiled-coil 1 (RSRC1) represses estrogen receptor beta (ERbeta) transcriptional activity via ERbeta SUMOylation. (PMID:25937118)
• This study demonstrated that RSRC1 mutation affects intellect and behaviour through aberrant splicing and transcription, downregulating IGFBP3. (PMID:29522154)
• RSRC1 rs6441201A allele was associated with increased neuroblastoma risk in Chinese children. (PMID:29653227)
• RSRC1 knockdown promoted the proliferation and migration of gastric cancer cells. In addition, the knockdown of RSRC1 decreased the expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), a potent tumor suppressor gene controlling cellular growth and viability. (PMID:31257492)
• Our findings support the pathogenic role of biallelic loss-of-function RSRC1 variants in autosomal recessive intellectual disability, in addition to contributing to the phenotypic delineation of this emerging condition (PMID:32227164)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Rsrc1	ENSMUSG00000034544
rattus_norvegicus	Rsrc1	ENSRNOG00000062777

Protein

Protein identifiers

Serine/Arginine-related protein 53 — Q96IZ7 (reviewed: Q96IZ7)

Alternative names: Arginine/serine-rich coiled-coil protein 1

All UniProt accessions (13): A0A804HIP2, A0A804HJC0, A0A804HJI2, A0A804HK29, A0A804HLK3, C9J367, C9J713, C9J8Q2, C9JVB3, Q96IZ7, F8WDM0, H7C558, H7C5Q0

UniProt curated annotations — full annotation on UniProt →

Function. Has a role in alternative splicing and transcription regulation. Involved in both constitutive and alternative pre-mRNA splicing. May have a role in the recognition of the 3’ splice site during the second step of splicing.

Subunit / interactions. Interacts (via Arg/Ser-rich domain) with LUC7L3, RBM39 and RSF1.

Subcellular location. Nucleus. Nucleus speckle. Cytoplasm.

Tissue specificity. Widely expressed. Expressed in brain, spinal cord, cerebellum.

Post-translational modifications. Phosphorylated.

Disease relevance. Intellectual developmental disorder, autosomal recessive 70 (MRT70) [MIM:618402] A form of intellectual disability, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT70 patients manifest impaired intellectual development, mild facial dysmorphism, febrile seizures, and behavioral abnormalities. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96IZ7-1	1	yes
Q96IZ7-2	2

RefSeq proteins (3): NP_001258763, NP_001258767, NP_057709 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR034604	SRRP53	Family

UniProt features (17 total): compositionally biased region 8, region of interest 3, sequence variant 2, chain 1, splice variant 1, sequence conflict 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96IZ7-F1	58.46	0.10

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 164 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, MULLIGHAN_NPM1_SIGNATURE_3_UP, TGCGCANK_UNKNOWN, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_ALTERNATIVE_MRNA_SPLICING_VIA_SPLICEOSOME, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, MITSIADES_RESPONSE_TO_APLIDIN_DN, CAGCTG_AP4_Q5, GOBP_NUCLEAR_TRANSPORT, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, TCF11_01, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_DN, GOBP_RNA_SPLICING, DODD_NASOPHARYNGEAL_CARCINOMA_UP, FISCHER_DREAM_TARGETS

GO Biological Process (6): alternative mRNA splicing, via spliceosome (GO:0000380), mRNA splicing, via spliceosome (GO:0000398), nucleocytoplasmic transport (GO:0006913), RNA splicing (GO:0008380), response to antibiotic (GO:0046677), mRNA processing (GO:0006397)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (3): nucleus (GO:0005634), cytoplasm (GO:0005737), nuclear speck (GO:0016607)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA processing	2
mRNA splicing, via spliceosome	1
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
nuclear transport	1
response to chemical	1
mRNA metabolic process	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1
nuclear ribonucleoprotein granule	1

Protein interactions and networks

STRING

3274 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RSRC1	RBM39	Q14498	911
RSRC1	LUC7L	Q9NQ29	855
RSRC1	U2AF1	Q01081	846
RSRC1	SRSF5	Q13243	796
RSRC1	SRSF2	Q01130	626
RSRC1	SRSF1	Q07955	619
RSRC1	RSRC2	Q7L4I2	533
RSRC1	SHOX2	O60902	525
RSRC1	MLF1	P58340	507
RSRC1	TMEM244	Q5VVB8	504
RSRC1	TMEM141	Q96I45	490
RSRC1	RPS9	P46781	487
RSRC1	RPS15	P11174	472
RSRC1	PUSL1	Q8N0Z8	467
RSRC1	HBS1L	Q9Y450	450

IntAct

97 interactions, top by confidence:

A	B	Type	Score
CDKN2A	CDK4	psi-mi:“MI:0914”(association)	0.960
SNRPE	GEMIN2	psi-mi:“MI:0914”(association)	0.770
COMMD1	VPS26C	psi-mi:“MI:0914”(association)	0.730
COMMD4	VPS26C	psi-mi:“MI:0914”(association)	0.730
NHP2	DKC1	psi-mi:“MI:0914”(association)	0.730
RSRC1	SRPK2	psi-mi:“MI:0217”(phosphorylation reaction)	0.690
CSNK2B	RPS6KA5	psi-mi:“MI:0914”(association)	0.660
COMMD6	VPS26C	psi-mi:“MI:0914”(association)	0.640
SF3B1	SAP18	psi-mi:“MI:0914”(association)	0.640
HDAC11	CLUH	psi-mi:“MI:0914”(association)	0.640
PHF20	KANSL1	psi-mi:“MI:0914”(association)	0.640
PPP2R3A	WTIP	psi-mi:“MI:0914”(association)	0.640
SRRM4	RSRC1	psi-mi:“MI:0915”(physical association)	0.560
LAMP2	RSRC1	psi-mi:“MI:0915”(physical association)	0.560
RAN	RSRC1	psi-mi:“MI:0915”(physical association)	0.560
PRPF40A	RSRC1	psi-mi:“MI:0915”(physical association)	0.560
YWHAG	SHTN1	psi-mi:“MI:0914”(association)	0.560
RSRC1	JMJD6	psi-mi:“MI:0914”(association)	0.550
JMJD6	RSRC1	psi-mi:“MI:0915”(physical association)	0.550
SMC1A	PDS5B	psi-mi:“MI:0914”(association)	0.530
SNRPE	SNRPGP15	psi-mi:“MI:0914”(association)	0.530
SRPK2	RRP9	psi-mi:“MI:0914”(association)	0.530
SNRNP40	AQR	psi-mi:“MI:0914”(association)	0.530
GNL3	IPO5	psi-mi:“MI:0914”(association)	0.480

BioGRID (147): RSRC1 (Affinity Capture-MS), RSRC1 (Affinity Capture-MS), RSRC1 (Affinity Capture-MS), TFIP11 (Affinity Capture-MS), C17orf85 (Affinity Capture-MS), PAXBP1 (Affinity Capture-MS), JMJD6 (Affinity Capture-MS), SNRNP40 (Affinity Capture-MS), CSNK2A1 (Affinity Capture-MS), CSNK2A2 (Affinity Capture-MS), RSRC1 (Affinity Capture-MS), RSRC1 (Affinity Capture-MS), RSRC1 (Affinity Capture-MS), RSRC1 (Affinity Capture-MS), RSRC1 (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: Q2T9Y0, Q5PPJ2, Q96IZ7, Q9DBU6

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 121 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
rRNA modification in the nucleus and cytosol	7	13.4×	8e-05
mRNA Polyadenylation	12	10.8×	2e-07
mRNA Splicing	9	10.1×	3e-05
Processing of Capped Intron-Containing Pre-mRNA	12	10.1×	4e-07
mRNA Splicing - Major Pathway	17	9.5×	1e-09
Major pathway of rRNA processing in the nucleolus and cytosol	14	8.8×	2e-07
CHD1 and CHD2 subfamily	7	7.8×	2e-03
Dengue Virus-Host Interactions	13	6.1×	3e-05

GO biological processes:

GO term	Partners	Fold	FDR
RNA splicing, via transesterification reactions	5	28.1×	9e-05
spliceosomal complex assembly	5	27.1×	9e-05
RNA processing	10	19.7×	6e-08
rRNA processing	11	14.0×	1e-07
mRNA splicing, via spliceosome	12	9.9×	8e-07
RNA splicing	12	9.5×	9e-07
defense response to virus	8	5.0×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	4
Uncertain significance	61
Likely benign	7
Benign	1

Top pathogenic / likely-pathogenic (11)

Variant ID	HGVS	Classification
1341490	NM_001271838.2(RSRC1):c.441_447dup (p.Glu150fs)	Pathogenic
1341491	NM_001271838.2(RSRC1):c.532-1G>A	Pathogenic
1341492	NM_001271838.2(RSRC1):c.3G>T (p.Met1Ile)	Pathogenic
626265	NM_001271838.2(RSRC1):c.268C>T (p.Arg90Ter)	Pathogenic
626266	NM_001271838.2(RSRC1):c.205C>T (p.Arg69Ter)	Pathogenic
985668	NM_001271838.2(RSRC1):c.194+1G>A	Pathogenic
985669	NM_001271838.2(RSRC1):c.495-2A>G	Pathogenic
2579470	NM_001271838.2(RSRC1):c.652+1G>A	Likely pathogenic
3064117	NM_001271838.2(RSRC1):c.332del (p.Arg111fs)	Likely pathogenic
3338217	NM_001271838.2(RSRC1):c.109C>T (p.Arg37Ter)	Likely pathogenic
4082565	NM_001271838.2(RSRC1):c.521T>G (p.Leu174Ter)	Likely pathogenic

SpliceAI

4435 predictions. Top by Δscore:

Variant	Effect	Δscore
3:158122094:T:G	acceptor_gain	1.0000
3:158122098:TATAG:T	acceptor_loss	1.0000
3:158122100:TA:T	acceptor_loss	1.0000
3:158122101:A:AG	acceptor_gain	1.0000
3:158122102:G:GT	acceptor_gain	1.0000
3:158122102:GA:G	acceptor_gain	1.0000
3:158122102:GAA:G	acceptor_gain	1.0000
3:158122102:GAAA:G	acceptor_gain	1.0000
3:158122102:GAAAT:G	acceptor_gain	1.0000
3:158122226:G:GT	donor_gain	1.0000
3:158122296:A:T	donor_gain	1.0000
3:158122296:AAGG:A	donor_loss	1.0000
3:158122297:AGGTG:A	donor_loss	1.0000
3:158122298:GGT:G	donor_loss	1.0000
3:158122300:T:G	donor_loss	1.0000
3:158123861:TTCA:T	acceptor_loss	1.0000
3:158123862:TCAG:T	acceptor_loss	1.0000
3:158123863:CA:C	acceptor_loss	1.0000
3:158123864:A:AG	acceptor_gain	1.0000
3:158123864:AGAC:A	acceptor_gain	1.0000
3:158123865:G:GA	acceptor_gain	1.0000
3:158123865:GAC:G	acceptor_gain	1.0000
3:158123865:GACG:G	acceptor_gain	1.0000
3:158123865:GACGC:G	acceptor_gain	1.0000
3:158123972:TCAAA:T	donor_gain	1.0000
3:158123988:GAAG:G	donor_gain	1.0000
3:158123993:T:G	donor_loss	1.0000
3:158124002:T:TG	donor_gain	1.0000
3:158136865:GATAA:G	donor_gain	1.0000
3:158203242:GTGG:G	donor_gain	1.0000

AlphaMissense

2148 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:158354894:T:A	V190D	0.999
3:158354897:T:A	L191H	0.999
3:158354897:T:C	L191P	0.999
3:158354902:G:C	A193P	0.999
3:158354905:G:C	A194P	0.999
3:158354906:C:A	A194D	0.999
3:158537139:G:C	A234P	0.999
3:158537172:T:C	F245L	0.999
3:158537174:C:A	F245L	0.999
3:158537174:C:G	F245L	0.999
3:158544184:T:C	L305S	0.999
3:158544216:T:A	W316R	0.999
3:158544216:T:C	W316R	0.999
3:158544218:G:C	W316C	0.999
3:158544218:G:T	W316C	0.999
3:158544229:T:C	L320S	0.999
3:158544238:T:C	L323P	0.999
3:158544253:T:C	L328P	0.999
3:158354885:T:C	L187P	0.998
3:158354908:G:C	A195P	0.998
3:158460940:G:C	A197P	0.998
3:158537143:T:A	I235N	0.998
3:158537157:T:C	F240L	0.998
3:158537159:T:A	F240L	0.998
3:158537159:T:G	F240L	0.998
3:158543477:C:A	A301D	0.998
3:158544241:G:C	R324P	0.998
3:158544258:G:C	G330R	0.998
3:158354883:A:C	R186S	0.997
3:158354883:A:T	R186S	0.997

dbSNP variants (sampled 300 via entrez): RS1000001387 (3:158266132 G>A), RS1000032029 (3:158464159 A>G,T), RS1000037384 (3:158439279 A>G), RS1000041254 (3:158253589 G>C), RS1000059772 (3:158509435 A>G,T), RS1000060240 (3:158383645 G>C,T), RS1000066039 (3:158150636 A>G,T), RS1000068814 (3:158259128 T>G), RS1000073151 (3:158527933 A>G), RS1000076533 (3:158204562 G>A), RS1000077361 (3:158151053 A>G), RS1000090695 (3:158509630 A>G), RS1000097608 (3:158210999 A>C), RS1000102315 (3:158281488 A>G), RS1000108549 (3:158412390 A>G)

Disease associations

OMIM: gene MIM:613352 | disease phenotypes: MIM:618402, MIM:181500, MIM:209850

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual developmental disorder, autosomal recessive 70	Definitive	Autosomal recessive
autosomal recessive non-syndromic intellectual disability	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Definitive	AR

Mondo (4): intellectual developmental disorder, autosomal recessive 70 (MONDO:0032729), schizophrenia (MONDO:0005090), autism (MONDO:0005260), autosomal recessive non-syndromic intellectual disability (MONDO:0019502)

Orphanet (1): NON RARE IN EUROPE: Schizophrenia (Orphanet:3140)

HPO phenotypes

18 total (20 of 18 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000020	Urinary incontinence
HP:0000252	Microcephaly
HP:0000278	Retrognathia
HP:0000316	Hypertelorism
HP:0000431	Wide nasal bridge
HP:0000729	Autistic behavior
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0002307	Drooling
HP:0002373	Febrile seizure (within the age range of 3 months to 6 years)
HP:0003593	Infantile onset
HP:0007018	Attention deficit hyperactivity disorder
HP:0025162	Severe temper tantrums
HP:0100753	Schizophrenia
HP:0000717	Autism

GWAS associations

22 associations (top):

Study	Trait	p-value
GCST001956_18	Height	2.000000e-09
GCST003989_31	Chin dimples	2.000000e-12
GCST004510_8	Sporadic neuroblastoma	1.000000e-11
GCST005232_8	Neuroticism	2.000000e-09
GCST005839_27	Depression	3.000000e-09
GCST005951_143	Body mass index	4.000000e-08
GCST006041_13	Major depressive disorder	1.000000e-08
GCST006190_42	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	2.000000e-08
GCST006190_68	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	2.000000e-07
GCST006192_15	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	5.000000e-12
GCST006192_29	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	9.000000e-10
GCST006193_25	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	4.000000e-08
GCST006193_66	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	6.000000e-07
GCST006195_29	Systolic blood pressure x smoking status (current vs non-current) interaction (2df test)	5.000000e-09
GCST006195_55	Systolic blood pressure x smoking status (current vs non-current) interaction (2df test)	4.000000e-11
GCST007429_111	Lung function (FVC)	3.000000e-26
GCST007432_126	FEV1	9.000000e-20
GCST007611_15	Chronic obstructive pulmonary disease or high blood pressure (pleiotropy)	1.000000e-09
GCST008661_3	Lung function in heavy smokers (high FEV1 vs average FEV1)	2.000000e-07
GCST009600_23	Anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, or Tourette syndrome (pleiotropy)	6.000000e-10
GCST010988_122	Adult body size	1.000000e-08
GCST90013421_29	Left-handedness	3.000000e-11

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0007660	neuroticism measurement
EFO:0004340	body mass index
EFO:0006336	diastolic blood pressure
EFO:0006527	smoking status measurement
EFO:0006335	systolic blood pressure
EFO:0004312	vital capacity
EFO:0004314	forced expiratory volume
EFO:0009902	handedness

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression	5
bisphenol A	increases expression, decreases methylation	2
Cisplatin	decreases expression, increases expression	2
Aflatoxin B1	affects expression, decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
dicrotophos	decreases expression	1
testosterone enanthate	affects expression	1
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
methacrylaldehyde	increases abundance, affects cotreatment, increases expression	1
beta-methylcholine	affects expression	1
torcetrapib	increases expression	1
abrine	decreases expression	1
bisphenol S	decreases methylation	1
Resveratrol	affects cotreatment, increases expression	1
Zoledronic Acid	decreases expression	1
Acrolein	affects cotreatment, increases expression, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases expression	1
Coumestrol	affects cotreatment, increases expression	1
Formaldehyde	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
N-Nitrosopyrrolidine	decreases expression	1
Ozone	increases abundance, affects cotreatment, increases expression	1
Quercetin	decreases expression	1
Valproic Acid	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Cyclosporine	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00000374	PHASE4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	PHASE4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	PHASE4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	PHASE4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	PHASE4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	PHASE4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	PHASE4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	PHASE4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	PHASE4	COMPLETED	The Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00044655	PHASE4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	PHASE4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia
NCT00053703	PHASE4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	PHASE4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	PHASE4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	PHASE4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	PHASE4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012	PHASE4	COMPLETED	Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776	PHASE4	COMPLETED	Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571	PHASE4	COMPLETED	Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368	PHASE4	COMPLETED	The Effects of Risperidone and Olanzapine on Thinking
NCT00114595	PHASE4	COMPLETED	Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923	PHASE4	COMPLETED	Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020	PHASE4	COMPLETED	Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder
NCT00140166	PHASE4	COMPLETED	Treatment of Acute Schizophrenia With Vitamin Therapy
NCT00145847	PHASE4	COMPLETED	Naltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148564	PHASE4	COMPLETED	Energy Homeostasis Under Treatment With Atypical Antipsychotics
NCT00156715	PHASE4	COMPLETED	Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder
NCT00158223	PHASE4	COMPLETED	Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
NCT00159081	PHASE4	COMPLETED	One Year Drug Treatment in First-Episode Schizophrenia
NCT00159120	PHASE4	COMPLETED	Maintenance Treatment vs. Stepwise Drug Discontinuation in First-Episode Schizophrenia
NCT00159133	PHASE4	COMPLETED	Prodrome-Based Early Intervention With Antipsychotics vs. Benzodiazepines in First-Episode Schizophrenia
NCT00159757	PHASE4	TERMINATED	12 Week Open, Non-Comparative Switch Study Of Oral Ziprazidone In Previously Treated Schizophrenic Patients
NCT00167817	PHASE4	COMPLETED	Effect of Switch to Aripiprazole on Health and Smoking Parameters in Patients With Schizophrenia: A Pilot Study
NCT00169026	PHASE4	TERMINATED	Alcoholism and Schizophrenia: Effects of Clozapine
NCT00169039	PHASE4	TERMINATED	Clozapine Versus Chlorpromazine for Treatment-Unresponsive Schizophrenia
NCT00169065	PHASE4	COMPLETED	Effectiveness of Clozapine Versus Olanzapine for Treatment-resistant Schizophrenia
NCT00169091	PHASE4	TERMINATED	Clozapine Versus Haloperidol for Treating the First Episode of Schizophrenia
NCT00176423	PHASE4	COMPLETED	Efficacy Study of Galantamine for Cognitive Impairments in Schizophrenia
NCT00176436	PHASE4	COMPLETED	Atomoxetine for Treatment of Weight Gain in Olanzapine or Clozapine Patients
NCT00177008	PHASE4	COMPLETED	Aripiprazole for the Treatment of Schizophrenia With Co-Morbid Social Anxiety