SCAPER

Summary

SCAPER (S-phase cyclin A associated protein in the ER, HGNC:13081) is a protein-coding gene on chromosome 15q24.3, encoding S phase cyclin A-associated protein in the endoplasmic reticulum (Q9BY12). CCNA2/CDK2 regulatory protein that transiently maintains CCNA2 in the cytoplasm.

Predicted to enable nucleic acid binding activity and zinc ion binding activity. Acts upstream of or within retina development in camera-type eye. Located in cytosol and nuclear speck.

Source: NCBI Gene 49855 — RefSeq curated summary.

At a glance

• Gene–disease (curated): intellectual developmental disorder and retinitis pigmentosa; IDDRP (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 11
• Clinical variants (ClinVar): 329 total — 8 pathogenic, 16 likely-pathogenic
• Phenotypes (HPO): 125
• MANE Select transcript: NM_020843

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13081
Approved symbol	SCAPER
Name	S-phase cyclin A associated protein in the ER
Location	15q24.3
Locus type	gene with protein product
Status	Approved
Aliases	Zfp291
Ensembl gene	ENSG00000140386
Ensembl biotype	protein_coding
OMIM	611611
Entrez	49855

Gene structure

Transcript identifiers

Ensembl transcripts: 32 — 19 protein_coding, 7 protein_coding_CDS_not_defined, 3 retained_intron, 3 nonsense_mediated_decay

ENST00000303521, ENST00000324767, ENST00000538941, ENST00000562890, ENST00000562948, ENST00000563246, ENST00000563290, ENST00000563688, ENST00000563919, ENST00000564022, ENST00000564177, ENST00000564590, ENST00000564757, ENST00000565372, ENST00000565507, ENST00000565970, ENST00000567601, ENST00000567618, ENST00000568382, ENST00000568428, ENST00000568549, ENST00000569395, ENST00000569784, ENST00000867407, ENST00000867408, ENST00000867409, ENST00000940730, ENST00000940731, ENST00000969236, ENST00000969237, ENST00000969238, ENST00000969239

RefSeq mRNA: 6 — MANE Select: NM_020843 NM_001145923, NM_001353009, NM_001353010, NM_001353011, NM_001353012, NM_020843

CCDS: CCDS53961, CCDS53962

Canonical transcript exons

ENST00000563290 — 32 exons

Exon	Start	End
ENSE00001155998	76376162	76376311
ENSE00001318153	76862416	76862533
ENSE00001326597	76381378	76381615
ENSE00002578771	76905299	76905340
ENSE00003485170	76574158	76574284
ENSE00003497347	76705903	76705984
ENSE00003504897	76621764	76621829
ENSE00003551790	76353949	76354140
ENSE00003571761	76504859	76504974
ENSE00003572430	76351237	76351288
ENSE00003573857	76471212	76471335
ENSE00003576737	76765337	76765454
ENSE00003580109	76434078	76434310
ENSE00003581796	76804533	76804633
ENSE00003582204	76665653	76665789
ENSE00003584546	76795280	76795440
ENSE00003588200	76857809	76857879
ENSE00003593004	76771742	76771954
ENSE00003605592	76766918	76767088
ENSE00003615205	76764961	76765072
ENSE00003623741	76733229	76733384
ENSE00003624841	76883812	76883876
ENSE00003627055	76765563	76765638
ENSE00003642358	76800248	76800364
ENSE00003654427	76728595	76728737
ENSE00003656364	76841734	76841931
ENSE00003658255	76774855	76775117
ENSE00003666685	76701758	76701865
ENSE00003677705	76702850	76703002
ENSE00003678431	76404524	76404679
ENSE00003692266	76753808	76753948
ENSE00003740378	76347904	76348736

Expression profiles

Bgee: expression breadth ubiquitous, 282 present calls, max score 95.68.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.0369 / max 588.4982, expressed in 1635 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
151022	10.8534	1610
151024	0.5279	211
151025	0.3871	177
151021	0.1273	47
151023	0.1124	62
151020	0.0287	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	95.68	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	95.61	gold quality
sural nerve	UBERON:0015488	94.38	gold quality
adrenal tissue	UBERON:0018303	93.61	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	93.50	gold quality
calcaneal tendon	UBERON:0003701	93.44	gold quality
buccal mucosa cell	CL:0002336	92.63	gold quality
ganglionic eminence	UBERON:0004023	91.82	gold quality
colonic epithelium	UBERON:0000397	91.30	gold quality
ventricular zone	UBERON:0003053	91.10	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	89.86	gold quality
popliteal artery	UBERON:0002250	89.72	gold quality
tibial artery	UBERON:0007610	89.72	gold quality
right frontal lobe	UBERON:0002810	88.45	gold quality
spinal cord	UBERON:0002240	88.16	gold quality
hypothalamus	UBERON:0001898	88.03	gold quality
adenohypophysis	UBERON:0002196	87.92	gold quality
gastrocnemius	UBERON:0001388	87.71	gold quality
cerebellar hemisphere	UBERON:0002245	87.68	gold quality
hindlimb stylopod muscle	UBERON:0004252	87.64	gold quality
Brodmann (1909) area 9	UBERON:0013540	87.62	gold quality
cerebellar cortex	UBERON:0002129	87.56	gold quality
pituitary gland	UBERON:0000007	87.50	gold quality
muscle of leg	UBERON:0001383	87.44	gold quality
cingulate cortex	UBERON:0003027	87.40	gold quality
right hemisphere of cerebellum	UBERON:0014890	87.40	gold quality
prefrontal cortex	UBERON:0000451	87.36	gold quality
aorta	UBERON:0000947	87.33	gold quality
right testis	UBERON:0004534	87.33	gold quality
anterior cingulate cortex	UBERON:0009835	87.27	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-7316	yes	36.86
E-GEOD-137537	yes	24.95
E-MTAB-7303	no	962.02
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

38 targeting SCAPER, 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-3646	100.00	73.56	5283
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-139-5P	99.80	69.50	1399
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-548AV-5P	99.60	70.84	2107
HSA-MIR-548K	99.60	70.84	2107
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-105-5P	99.54	69.24	2060
HSA-MIR-7853-5P	99.54	69.30	2055
HSA-MIR-543	99.52	69.03	2595
HSA-MIR-8054	99.48	70.81	2084
HSA-MIR-372-5P	99.41	69.11	2299
HSA-MIR-5697	99.39	67.74	1249
HSA-MIR-888-5P	99.30	70.15	1855
HSA-MIR-1264	99.25	66.81	1317
HSA-MIR-505-3P	99.19	69.71	896
HSA-MIR-4528	99.18	69.77	1936
HSA-MIR-4426	99.17	66.74	1949
HSA-MIR-4520-2-3P	99.14	69.28	1009
HSA-MIR-548L	99.06	70.90	2560

Literature-anchored findings (GeneRIF, showing 9)

• An unstable CCTG repeat in the second intron of the ZNF291 gene, on chromosome 15q21-24, was identified. (PMID:17553665)
• Study describes the biochemically purification and identification of SCAPER, a novel protein that specifically interacts with cyclin A/Cdk2 in vivo. (PMID:17698606)
• By sequestering cyclin A/Cdk2, SCAPER is capable of directing the activity of this kinase complex away from the nucleus and regulating cyclin A/Cdk2 equilibrium in distinct subcellular compartments. (PMID:18245951)
• Unique to our patient’s presentation is the absence of intellectual disability and attention-deficit/hyperactivity disorder, suggesting that SCAPER-associated retinitis pigmentosa can also present without systemic manifestations. (PMID:30561111)
• As SCAPER expression is known to peak at late G1 and S phase, overlapping the timing of ciliary resorption, our data suggest a possible role of SCAPER in ciliary dynamics and disassembly, also affecting microtubule-related mitotic progression. (PMID:30723319)
• Homozygous variants in the gene SCAPER cause syndromic intellectual disability. (PMID:31069901)
• Delineating the expanding phenotype associated with SCAPER gene mutation. (PMID:31192531)
• Male sterility and reduced female fertility in SCAPER-deficient mice. (PMID:32510560)
• Absence of SCAPER causes male infertility in humans and Drosophila by modulating microtubule dynamics during meiosis. (PMID:32527956)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	scaper	ENSDARG00000023104
mus_musculus	Scaper	ENSMUSG00000034007
rattus_norvegicus	Scaper	ENSRNOG00000006864
drosophila_melanogaster	ssp3	FBGN0032723
caenorhabditis_elegans	scpr-1	WBGENE00012389

Protein

Protein identifiers

S phase cyclin A-associated protein in the endoplasmic reticulum — Q9BY12 (reviewed: Q9BY12)

Alternative names: Zinc finger protein 291

All UniProt accessions (11): Q9BY12, H3BPB0, H3BPM0, H3BQ61, H3BQF3, H3BR40, H3BS25, H3BT27, H3BTL8, H3BTY2, H3BU24

UniProt curated annotations — full annotation on UniProt →

Function. CCNA2/CDK2 regulatory protein that transiently maintains CCNA2 in the cytoplasm.

Subunit / interactions. Interacts with CCNA2/CDK2 complex, but not with CCNA2/CDC2, CCNB1/CDC2 or CCNE1/CDK2 complexes, at multiple phases of the cell cycle, including S and G2/M.

Subcellular location. Endoplasmic reticulum. Nucleus.

Tissue specificity. Widely expressed with high expression in testis. Isoform 1 is detected in various tissues, including retina, fetal and adult brain. Isoform 2 is expressed in the retina at high levels, and in the brain at very low levels.

Post-translational modifications. Phosphorylated in vitro by the CCNA2/CDK2 complex.

Disease relevance. Intellectual developmental disorder and retinitis pigmentosa (IDDRP) [MIM:618195] An autosomal recessive disease characterized by mild to moderate intellectual disability, retinitis pigmentosa, and attention deficit-hyperactivity disorder observed in some patients. The disease may be caused by variants affecting the gene represented in this entry.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9BY12-1	1	yes
Q9BY12-3	3

RefSeq proteins (6): NP_001139395, NP_001339938, NP_001339939, NP_001339940, NP_001339941, NP_065894* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003604	Matrin/U1-like-C_Znf_C2H2	Domain
IPR013087	Znf_C2H2_type	Domain
IPR032446	SCAPER_N	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily

Pfam: PF12874, PF16501

UniProt features (20 total): sequence variant 5, region of interest 4, mutagenesis site 3, sequence conflict 2, compositionally biased region 2, chain 1, zinc finger region 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
8BPO	ELECTRON MICROSCOPY	2.8
9HJ1	ELECTRON MICROSCOPY	2.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BY12-F1	68.35	0.25

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 (1): 832

Mutagenesis-validated functional residues (3):

Position	Phenotype
26–28	no effect on ccna2/cdk2 complex-binding.
199–201	loss of ccna2/cdk2 complex-binding.
678–680	no effect on ccna2/cdk2 complex-binding.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 364 (showing top): MORF_FLT1, MORF_ESR1, ZHAN_MULTIPLE_MYELOMA_HP_UP, MILI_PSEUDOPODIA_CHEMOTAXIS_UP, GOBP_SENSORY_ORGAN_DEVELOPMENT, MODULE_48, GOBP_RETINA_DEVELOPMENT_IN_CAMERA_TYPE_EYE, MODULE_95, IVANOVA_HEMATOPOIESIS_STEM_CELL_LONG_TERM, MORF_PRKACA, GOCC_NUCLEAR_SPECK, GOCC_NUCLEAR_BODY, GOCC_RIBONUCLEOPROTEIN_GRANULE, MORF_MYC, BLALOCK_ALZHEIMERS_DISEASE_DN

GO Biological Process (5): antral ovarian follicle growth (GO:0001547), spermatogenesis (GO:0007283), retina development in camera-type eye (GO:0060041), seminiferous tubule development (GO:0072520), ovarian follicle development (GO:0001541)

GO Molecular Function (4): nucleic acid binding (GO:0003676), zinc ion binding (GO:0008270), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (8): nucleoplasm (GO:0005654), endoplasmic reticulum (GO:0005783), cytosol (GO:0005829), nuclear speck (GO:0016607), sperm head (GO:0061827), ooplasm (GO:1990917), nucleus (GO:0005634), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cytoplasm	3
developmental process involved in reproduction	2
anatomical structure development	2
binding	2
intracellular membrane-bounded organelle	2
ovarian follicle development	1
ovulation cycle process	1
developmental growth	1
male gamete generation	1
camera-type eye development	1
male gonad development	1
tube development	1
reproductive structure development	1
female gonad development	1
transition metal ion binding	1
cation binding	1
nuclear lumen	1
endomembrane system	1
nuclear ribonucleoprotein granule	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

640 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SCAPER	CCNA1	P78396	833
SCAPER	CCNA2	P20248	826
SCAPER	CDK2	P24941	682
SCAPER	RCN2	Q14257	540
SCAPER	ATOSB	Q7L5A3	507
SCAPER	CCNL2	Q96S94	505
SCAPER	ISL2	Q96A47	487
SCAPER	GSG1	Q2KHT4	477
SCAPER	NBAS	A2RRP1	471
SCAPER	TSPAN3	O60637	432
SCAPER	CEP126	Q9P2H0	431
SCAPER	IARS2	Q9NSE4	423
SCAPER	EHBP1	Q8NDI1	422
SCAPER	INSIG1	O15503	422
SCAPER	DNMBP	Q6XZF7	416

IntAct

27 interactions, top by confidence:

A	B	Type	Score
SCAPER	CCNA2	psi-mi:“MI:0915”(physical association)	0.740
CCNA2	GMNN	psi-mi:“MI:0914”(association)	0.640
N	NOP56	psi-mi:“MI:0914”(association)	0.530
N	RBM47	psi-mi:“MI:0914”(association)	0.530
SCAPER	CDK2	psi-mi:“MI:0915”(physical association)	0.520
SCAPER	CCAR1	psi-mi:“MI:0915”(physical association)	0.400
APPL1	SCAPER	psi-mi:“MI:0915”(physical association)	0.370
CELSR3	SCAPER	psi-mi:“MI:0915”(physical association)	0.370
MEGF10	SCAPER	psi-mi:“MI:0915”(physical association)	0.370
CCNA2	ZC3H18	psi-mi:“MI:0914”(association)	0.350
MZT1	ZC3H18	psi-mi:“MI:0914”(association)	0.350
DICER1	IGF2BP3	psi-mi:“MI:0914”(association)	0.350
CCNA2	TBC1D4	psi-mi:“MI:0914”(association)	0.350
BMI1	HMGB1P1	psi-mi:“MI:0914”(association)	0.350
N	RBM47	psi-mi:“MI:0914”(association)	0.350
DYRK1A	TEX13D	psi-mi:“MI:0914”(association)	0.350
HMGN5	SMCHD1	psi-mi:“MI:0914”(association)	0.350
PIP	RBM47	psi-mi:“MI:0914”(association)	0.350

BioGRID (44): SCAPER (Affinity Capture-MS), SCAPER (Two-hybrid), SCAPER (Affinity Capture-MS), SCAPER (Affinity Capture-MS), SCAPER (Affinity Capture-MS), SCAPER (Affinity Capture-MS), SCAPER (Affinity Capture-RNA), SCAPER (Affinity Capture-RNA), SCAPER (Affinity Capture-MS), SCAPER (Affinity Capture-MS), SCAPER (Proximity Label-MS), SCAPER (Proximity Label-MS), SCAPER (Proximity Label-MS), SCAPER (Proximity Label-MS), SCAPER (Affinity Capture-MS)

ESM2 similar proteins: A0JN62, A2RT67, A2RUS2, A2VDU2, A4IFB6, A4IIM3, A7MBL8, B1H2P5, B4F779, O94967, P48553, Q08CL8, Q0VEJ0, Q14161, Q15650, Q3TLI0, Q4R350, Q5RAQ5, Q5RCP7, Q5RDV5, Q5TKA1, Q5XIA4, Q5ZIW2, Q5ZJK1, Q68CZ1, Q6AYF1, Q6QD73, Q7TSG1, Q7ZYH1, Q8BH15, Q8BIK4, Q8BKH7, Q8C735, Q8CG73, Q8CGF6, Q8IWR0, Q8IZQ1, Q8N6S4, Q8N960, Q8NEU8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	8
Likely pathogenic	16
Uncertain significance	185
Likely benign	54
Benign	20

Top pathogenic / likely-pathogenic (24)

Variant ID	HGVS	Classification
2300926	NM_020843.4(SCAPER):c.2436del (p.Arg814fs)	Pathogenic
3544437	NM_020843.4(SCAPER):c.1461_1462insGTGGTATATCC (p.Met488fs)	Pathogenic
417685	NM_020843.3(SCAPER):c.2973_2976del (p.Ile991Metfs)	Pathogenic
424861	NM_020843.4(SCAPER):c.2023-2A>G	Pathogenic
548448	NM_020843.4(SCAPER):c.2806del (p.Thr935_Leu936insTer)	Pathogenic
620525	NM_020843.4(SCAPER):c.2377C>T (p.Gln793Ter)	Pathogenic
800544	NM_020843.4(SCAPER):c.2236dup (p.Ile746fs)	Pathogenic
800545	NM_020843.4(SCAPER):c.2179C>T (p.Arg727Ter)	Pathogenic
1325035	NM_020843.4(SCAPER):c.2961_2962del (p.Cys988fs)	Likely pathogenic
1325036	NM_020843.4(SCAPER):c.2955-1G>T	Likely pathogenic
1334384	NM_020843.4(SCAPER):c.334C>T (p.Arg112Ter)	Likely pathogenic
1676479	NM_020843.4(SCAPER):c.125-1G>A	Likely pathogenic
2631669	NM_020843.4(SCAPER):c.2444_2445dup (p.His816fs)	Likely pathogenic
3065980	NM_020843.4(SCAPER):c.2364T>A (p.Tyr788Ter)	Likely pathogenic
3248655	NM_020843.4(SCAPER):c.2613dup (p.Ala872fs)	Likely pathogenic
3358415	NM_020843.4(SCAPER):c.306C>G (p.Tyr102Ter)	Likely pathogenic
4087726	NM_020843.4(SCAPER):c.2605A>T (p.Lys869Ter)	Likely pathogenic
800546	NM_020843.4(SCAPER):c.1116del (p.Val373fs)	Likely pathogenic
800547	NM_020843.4(SCAPER):c.1495+1G>A	Likely pathogenic
800549	NM_020843.4(SCAPER):c.829C>T (p.Arg277Ter)	Likely pathogenic
800550	NM_020843.4(SCAPER):c.3707_3708del (p.Ser1236fs)	Likely pathogenic
800551	NM_020843.4(SCAPER):c.2166-3C>G	Likely pathogenic
829945	NM_020843.4(SCAPER):c.2653del (p.Glu885fs)	Likely pathogenic
829946	NM_020843.4(SCAPER):c.1081C>T (p.Arg361Ter)	Likely pathogenic

SpliceAI

7601 predictions. Top by Δscore:

Variant	Effect	Δscore
15:76351232:CATA:C	donor_loss	1.0000
15:76351233:ATAC:A	donor_loss	1.0000
15:76351234:TA:T	donor_loss	1.0000
15:76351235:A:AC	donor_gain	1.0000
15:76351236:C:CC	donor_gain	1.0000
15:76351236:C:CG	donor_loss	1.0000
15:76351286:ATC:A	acceptor_gain	1.0000
15:76351286:ATCC:A	acceptor_loss	1.0000
15:76351287:TC:T	acceptor_gain	1.0000
15:76351288:CCTG:C	acceptor_gain	1.0000
15:76351289:C:A	acceptor_loss	1.0000
15:76351289:C:CC	acceptor_gain	1.0000
15:76351290:T:A	acceptor_loss	1.0000
15:76353945:GTAC:G	donor_loss	1.0000
15:76353948:CCTG:C	donor_loss	1.0000
15:76353981:T:C	donor_gain	1.0000
15:76354136:ATCAC:A	acceptor_gain	1.0000
15:76354137:TCAC:T	acceptor_gain	1.0000
15:76354138:CAC:C	acceptor_gain	1.0000
15:76354138:CACC:C	acceptor_gain	1.0000
15:76354139:AC:A	acceptor_gain	1.0000
15:76354139:ACC:A	acceptor_loss	1.0000
15:76354140:CC:C	acceptor_gain	1.0000
15:76354141:C:CC	acceptor_gain	1.0000
15:76354146:A:AC	acceptor_gain	1.0000
15:76376157:CTTA:C	donor_loss	1.0000
15:76376158:TTA:T	donor_loss	1.0000
15:76376159:TA:T	donor_loss	1.0000
15:76376160:ACCTG:A	donor_loss	1.0000
15:76376161:C:A	donor_loss	1.0000

AlphaMissense

9265 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:76702947:G:T	A768D	1.000
15:76702980:T:G	H757P	1.000
15:76702981:G:C	H757D	1.000
15:76702982:C:A	R756S	1.000
15:76702982:C:G	R756S	1.000
15:76702986:C:G	R755P	1.000
15:76705903:C:A	K749N	1.000
15:76705903:C:G	K749N	1.000
15:76705913:A:C	I746S	1.000
15:76705913:A:G	I746T	1.000
15:76705938:C:G	A738P	1.000
15:76705950:C:G	A734P	1.000
15:76705953:C:G	A733P	1.000
15:76705958:A:G	L731P	1.000
15:76705962:C:G	A730P	1.000
15:76705965:C:G	A729P	1.000
15:76705970:C:G	R727P	1.000
15:76728622:C:G	R713P	1.000
15:76728716:C:G	A682P	1.000
15:76728733:C:G	R676P	1.000
15:76733296:A:G	L652P	1.000
15:76733338:C:G	R638P	1.000
15:76733347:T:G	Q635P	1.000
15:76733351:C:G	A634P	1.000
15:76733356:A:G	L632P	1.000
15:76733356:A:T	L632H	1.000
15:76733365:A:C	I629R	1.000
15:76733365:A:G	I629T	1.000
15:76733365:A:T	I629K	1.000
15:76733367:A:C	F628L	1.000

dbSNP variants (sampled 300 via entrez): RS1000001391 (15:76764028 T>C), RS1000003372 (15:76511819 G>A), RS1000006348 (15:76502576 G>C), RS1000010786 (15:76706617 G>C,T), RS1000015963 (15:76688156 C>T), RS1000021946 (15:76792382 A>C), RS1000023792 (15:76725555 A>G), RS1000024995 (15:76401122 T>C), RS1000027332 (15:76878349 C>T), RS1000031834 (15:76584401 A>C), RS1000032759 (15:76691037 T>G), RS1000035026 (15:76602150 G>A,C), RS1000059978 (15:76843878 T>C), RS1000063697 (15:76541141 T>C,G), RS1000064299 (15:76505158 G>A,C)

Disease associations

OMIM: gene MIM:611611 | disease phenotypes: MIM:618195, MIM:181500, MIM:268000

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual developmental disorder and retinitis pigmentosa; IDDRP	Strong	Autosomal recessive
neurodevelopmental disorder	Strong	Autosomal recessive
Bardet-Biedl syndrome	Supportive	Autosomal recessive
retinitis pigmentosa	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
intellectual developmental disorder and retinitis pigmentosa; IDDRP	Definitive	AR

Mondo (11): intellectual developmental disorder and retinitis pigmentosa; IDDRP (MONDO:0032594), schizophrenia (MONDO:0005090), inherited retinal dystrophy (MONDO:0019118), optic atrophy (MONDO:0003608), attention deficit-hyperactivity disorder (MONDO:0007743), retinitis pigmentosa (MONDO:0019200), intellectual disability (MONDO:0001071), obesity disorder (MONDO:0011122), brachydactyly (MONDO:0021004), Bardet-Biedl syndrome (MONDO:0015229), neurodevelopmental disorder (MONDO:0700092)

Orphanet (7): OBSOLETE: Inherited retinal disorder (Orphanet:71862), Retinitis pigmentosa (Orphanet:791), OBSOLETE: Syndromic rod-cone dystrophy (Orphanet:98661), Obesity due to melanocortin 4 receptor deficiency (Orphanet:71529), NON RARE IN EUROPE: Schizophrenia (Orphanet:3140), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658), NON RARE IN EUROPE: Non rare obesity (Orphanet:521399)

HPO phenotypes

125 total (30 of 125 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000011	Neurogenic bladder
HP:0000028	Cryptorchidism
HP:0000076	Vesicoureteral reflux
HP:0000085	Horseshoe kidney
HP:0000100	Nephrotic syndrome
HP:0000119	Abnormality of the genitourinary system
HP:0000126	Hydronephrosis
HP:0000135	Hypogonadism
HP:0000147	Polycystic ovaries
HP:0000163	Abnormal oral cavity morphology
HP:0000218	High palate
HP:0000278	Retrognathia
HP:0000316	Hypertelorism
HP:0000343	Long philtrum
HP:0000358	Posteriorly rotated ears
HP:0000365	Hearing impairment
HP:0000388	Otitis media
HP:0000400	Macrotia
HP:0000405	Conductive hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000426	Prominent nasal bridge
HP:0000470	Short neck
HP:0000483	Astigmatism
HP:0000486	Strabismus
HP:0000494	Downslanted palpebral fissures
HP:0000501	Glaucoma
HP:0000505	Visual impairment
HP:0000512	Abnormal electroretinogram
HP:0000518	Cataract

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST002880_5	Recalcitrant atopic dermatitis	3.000000e-07
GCST003815_71	Late-onset Alzheimer’s disease	2.000000e-06
GCST003815_89	Late-onset Alzheimer’s disease	3.000000e-06
GCST006940_136	Neurociticism	2.000000e-10
GCST008058_253	Estimated glomerular filtration rate	5.000000e-13
GCST008059_18	Estimated glomerular filtration rate	2.000000e-15
GCST008522_87	Bitter alcoholic beverage consumption	6.000000e-06
GCST008972_25	Urate levels	4.000000e-09
GCST011780_13	Neonatal white matter microstructure	5.000000e-06
GCST012276_16	Clostridioides difficle infection in antibiotics-users	7.000000e-06
GCST90000025_225	Appendicular lean mass	2.000000e-09

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:1000651	recalcitrant atopic dermatitis
EFO:1001870	late-onset Alzheimers disease
EFO:0007660	neuroticism measurement
EFO:0010092	bitter alcoholic beverage consumption measurement
EFO:0004531	urate measurement
EFO:0005674	white matter microstructure measurement
EFO:0009130	clostridium difficile infection
EFO:0004980	appendicular lean mass

MeSH disease descriptors (7)

Descriptor	Name	Tree numbers
D020788	Bardet-Biedl Syndrome	C10.228.140.617.200; C11.270.684.624; C16.131.077.245.125; C16.320.184.125
D059327	Brachydactyly	C05.660.585.262; C16.131.621.585.262
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886	Neurodevelopmental Disorders	F03.625
D009896	Optic Atrophy	C10.292.700.225; C11.640.451
D058499	Retinal Dystrophies	C11.768.585.658
D012174	Retinitis Pigmentosa	C11.270.684; C11.768.585.658.500; C16.320.290.684

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases expression	5
Benzo(a)pyrene	decreases expression	3
Aflatoxin B1	affects expression, decreases expression, increases methylation	3
potassium chromate(VI)	affects cotreatment, decreases expression	2
entinostat	decreases expression, affects cotreatment	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
methylmercuric chloride	decreases expression	1
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
trichostatin A	decreases expression, increases expression	1
sodium arsenite	increases expression	1
butyraldehyde	decreases expression	1
epigallocatechin gallate	decreases expression, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	decreases expression	1
CGP 52608	increases reaction, affects binding	1
systhane	affects response to substance	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	increases methylation	1
jinfukang	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Vorinostat	decreases expression	1
Leflunomide	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression	1
Arsenic	affects methylation	1
Caffeine	decreases phosphorylation	1
Calcitriol	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D8UZ	Ubigene HCT 116 SCAPER KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00717080	PHASE4	COMPLETED	The Role of Capsular Tension Ring (CTR) in Anterior Capsular Contraction
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,
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