SPTBN5

Summary

SPTBN5 (spectrin beta, non-erythrocytic 5, HGNC:15680) is a protein-coding gene on chromosome 15q21, encoding Spectrin beta chain, non-erythrocytic 5 (Q9NRC6).

Enables cytoskeletal protein binding activity; dynein intermediate chain binding activity; and identical protein binding activity. Acts upstream of or within Golgi organization and lysosomal transport. Located in cytoplasm; photoreceptor connecting cilium; and photoreceptor disc membrane.

Source: NCBI Gene 51332 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Limited, GenCC)
• GWAS associations: 9
• Clinical variants (ClinVar): 954 total
• Phenotypes (HPO): 1
• MANE Select transcript: NM_016642

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15680
Approved symbol	SPTBN5
Name	spectrin beta, non-erythrocytic 5
Location	15q21
Locus type	gene with protein product
Status	Approved
Aliases	HUSPECV, BSPECV, HUBSPECV
Ensembl gene	ENSG00000137877
Ensembl biotype	protein_coding
OMIM	605916
Entrez	51332

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 retained_intron

ENST00000320955, ENST00000563899

RefSeq mRNA: 1 — MANE Select: NM_016642 NM_016642

CCDS: CCDS61599

Canonical transcript exons

ENST00000320955 — 68 exons

Exon	Start	End
ENSE00000931047	41851283	41851369
ENSE00000931048	41851779	41851850
ENSE00000931050	41852634	41852735
ENSE00000931051	41852824	41853000
ENSE00000931079	41868398	41868601
ENSE00000931080	41869841	41870020
ENSE00000931081	41870243	41870353
ENSE00000931082	41870446	41870560
ENSE00000931083	41871375	41871520
ENSE00000931084	41871782	41871917
ENSE00000931085	41872302	41872459
ENSE00000931086	41873492	41873608
ENSE00000931087	41873845	41874045
ENSE00000931088	41874292	41874478
ENSE00000931089	41874842	41875056
ENSE00001107107	41887213	41887441
ENSE00001107111	41890089	41890205
ENSE00001107126	41882996	41883228
ENSE00001107136	41877116	41877356
ENSE00001107141	41878342	41878629
ENSE00001107146	41885735	41886366
ENSE00001107154	41882269	41882469
ENSE00001107163	41876548	41876647
ENSE00001107167	41876114	41876284
ENSE00001107172	41876809	41876948
ENSE00001107186	41882585	41882738
ENSE00001107199	41887928	41888085
ENSE00001107206	41881034	41881234
ENSE00001107215	41892894	41893061
ENSE00001107224	41880160	41880312
ENSE00001107228	41883348	41883486
ENSE00001107242	41881936	41882145
ENSE00001107270	41879734	41879864
ENSE00001150863	41875458	41875622
ENSE00001150889	41879260	41879499
ENSE00001151052	41853258	41853447
ENSE00001205299	41850854	41850939
ENSE00001205302	41851059	41851150
ENSE00001205315	41852182	41852316
ENSE00001205330	41853582	41853787
ENSE00001205333	41854050	41854205
ENSE00001205336	41854782	41854976
ENSE00001205339	41855224	41855428
ENSE00001205343	41855549	41855745
ENSE00001205347	41856386	41856598
ENSE00001205350	41856853	41857039
ENSE00001205351	41857238	41857494
ENSE00001205355	41857573	41857710
ENSE00001205357	41858602	41858748
ENSE00001205362	41858890	41858980
ENSE00001205366	41860586	41860758
ENSE00001205368	41861419	41861496
ENSE00001205371	41861735	41861923
ENSE00001205375	41862130	41862292
ENSE00001205378	41862539	41862660
ENSE00001205382	41862790	41862903
ENSE00001205384	41863704	41863818
ENSE00001205387	41863909	41864024
ENSE00001205392	41865808	41865903
ENSE00001205394	41866038	41866229
ENSE00001205398	41866344	41866493
ENSE00001205401	41866959	41867126
ENSE00001222300	41867538	41867642
ENSE00001222551	41893282	41893546
ENSE00001355853	41848146	41848628
ENSE00001355857	41893899	41894053
ENSE00001375738	41849869	41849959
ENSE00001380130	41868069	41868218

Expression profiles

Bgee: expression breadth ubiquitous, 162 present calls, max score 94.45.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0665 / max 25.0898, expressed in 21 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
149533	0.0397	13
149535	0.0161	6
149534	0.0062	5
149536	0.0046	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	94.45	gold quality
cerebellar hemisphere	UBERON:0002245	84.08	gold quality
right hemisphere of cerebellum	UBERON:0014890	84.03	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.94	gold quality
tibial nerve	UBERON:0001323	83.84	gold quality
cerebellar cortex	UBERON:0002129	83.77	gold quality
lower esophagus mucosa	UBERON:0035834	81.74	gold quality
cerebellum	UBERON:0002037	81.57	gold quality
olfactory bulb	UBERON:0002264	76.36	silver quality
apex of heart	UBERON:0002098	76.18	gold quality
type B pancreatic cell	CL:0000169	74.33	gold quality
mucosa of paranasal sinus	UBERON:0005030	73.76	gold quality
male germ cell	CL:0000015	72.79	gold quality
sperm	CL:0000019	72.42	gold quality
ileal mucosa	UBERON:0000331	71.21	silver quality
esophagus mucosa	UBERON:0002469	70.68	gold quality
mucosa of urinary bladder	UBERON:0001259	69.90	gold quality
nasal cavity epithelium	UBERON:0005384	69.10	gold quality
pigmented layer of retina	UBERON:0001782	68.97	gold quality
skin of abdomen	UBERON:0001416	68.90	gold quality
pancreatic ductal cell	CL:0002079	68.89	silver quality
granulocyte	CL:0000094	68.49	gold quality
heart left ventricle	UBERON:0002084	68.26	gold quality
cardiac ventricle	UBERON:0002082	67.82	gold quality
right lobe of thyroid gland	UBERON:0001119	67.62	gold quality
right lobe of liver	UBERON:0001114	67.61	gold quality
metanephros cortex	UBERON:0010533	67.43	gold quality
tibialis anterior	UBERON:0001385	67.11	silver quality
skin of leg	UBERON:0001511	66.89	gold quality
trigeminal ganglion	UBERON:0001675	66.85	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	5.24

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

18 targeting SPTBN5, 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-7152-3P	99.97	67.47	849
HSA-MIR-6727-3P	99.49	65.92	1333
HSA-MIR-4687-3P	99.48	66.41	968
HSA-MIR-12132	99.47	68.90	1341
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-4722-3P	99.35	65.22	1099
HSA-MIR-3191-5P	99.24	66.52	1722
HSA-MIR-6809-5P	99.13	68.45	1223
HSA-MIR-942-3P	98.81	69.04	876
HSA-MIR-6731-3P	98.61	67.86	749
HSA-MIR-210-5P	98.57	64.37	832
HSA-MIR-4718	98.55	68.61	814
HSA-MIR-924	97.78	66.21	681
HSA-MIR-4786-5P	97.45	67.89	924
HSA-MIR-645	97.28	66.30	486
HSA-MIR-6508-3P	96.73	65.48	576
HSA-MIR-500B-3P	96.49	65.40	1087
HSA-MIR-2861	95.24	65.47	1056

Literature-anchored findings (GeneRIF, showing 4)

• interaction of hTRPC4 with alphaII-spectrin and betaV-spectrin was confirmed by glutathione S-transferase pulldown and co-immunoprecipitation experiments (PMID:18048348)
• The initial chi-square test revealed that the Cright curved arrow T polymorphism of CLEC16A and the Aright curved arrow G polymorphism of SPTBN5 were significantly ssociated with ischemic stroke among individuals with metabolic syndrome. (PMID:20043139)
• study identified spectrin betaV as a myosin VIIa- and rhodopsin-interacting partner in photoreceptor cells; suggest that spectrin betaV homomers couple some USH1 proteins, opsin and other phototransduction proteins to both actin- and microtubule-based motors, thereby contributing to their transport towards the photoreceptor outer disks (PMID:23704327)
• Adaptive mutations of spectrin-betaV occurred in the mammalian lineage and were accompanied with substantial changes in the protein distribution within inner ear hair cells. (PMID:28179572)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	sptbn5	ENSDARG00000097683
mus_musculus	Sptbn5	ENSMUSG00000074899
rattus_norvegicus	Sptbn5	ENSRNOG00000059260
drosophila_melanogaster	kst	FBGN0004167
caenorhabditis_elegans		WBGENE00004855

Paralogs (36): SYNE2 (ENSG00000054654), SPTB (ENSG00000070182), ACTN1 (ENSG00000072110), ACTN2 (ENSG00000077522), DSP (ENSG00000096696), DRP2 (ENSG00000102385), SPTBN1 (ENSG00000115306), MACF1 (ENSG00000127603), FLNC (ENSG00000128591), ACTN4 (ENSG00000130402), SYNE1 (ENSG00000131018), MICAL2 (ENSG00000133816), DTNA (ENSG00000134769), MICAL1 (ENSG00000135596), FLNB (ENSG00000136068), DTNB (ENSG00000138101), GAS2L3 (ENSG00000139354), DST (ENSG00000151914), UTRN (ENSG00000152818), SPTBN4 (ENSG00000160460), SPTA1 (ENSG00000163554), CLMN (ENSG00000165959), PKHD1 (ENSG00000170927), SPTBN2 (ENSG00000173898), SYNE3 (ENSG00000176438), PLEC (ENSG00000178209), SMTNL2 (ENSG00000188176), FLNA (ENSG00000196924), SPTAN1 (ENSG00000197694), DMD (ENSG00000198947), PKHD1L1 (ENSG00000205038), DYTN (ENSG00000232125), MICAL3 (ENSG00000243156), ACTN3 (ENSG00000248746), EPPK1 (ENSG00000261150), GAS2L2 (ENSG00000270765)

Protein

Protein identifiers

Spectrin beta chain, non-erythrocytic 5 — Q9NRC6 (reviewed: Q9NRC6)

Alternative names: Beta-V spectrin

All UniProt accessions (1): Q9NRC6

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Probably associates with an alpha chain. Interacts (via C-terminus) with TRPC4.

Subcellular location. Cytoplasm. Cytoskeleton.

Tissue specificity. Expressed at very low levels in many tissues, with strongest expression in cerebellum, spinal cord, stomach, pituitary gland, liver, pancreas, salivary gland, kidney, bladder, and heart.

Similarity. Belongs to the spectrin family.

RefSeq proteins (1): NP_057726* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001589	Actinin_actin-bd_CS	Conserved_site
IPR001715	CH_dom	Domain
IPR001849	PH_domain	Domain
IPR002017	Spectrin_repeat	Repeat
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR018159	Spectrin/alpha-actinin	Repeat
IPR036872	CH_dom_sf	Homologous_superfamily

Pfam: PF00169, PF00307, PF00435

UniProt features (43 total): repeat 27, sequence variant 4, sequence conflict 4, domain 3, region of interest 3, chain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

No AlphaFold model available for Q9NRC6 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

Function

Pathways and Gene Ontology

Reactome pathways

18 pathways

ID	Pathway
R-HSA-375165	NCAM signaling for neurite out-growth
R-HSA-445095	Interaction between L1 and Ankyrins
R-HSA-5673001	RAF/MAP kinase cascade
R-HSA-6807878	COPI-mediated anterograde transport
R-HSA-1266738	Developmental Biology
R-HSA-162582	Signal Transduction
R-HSA-199977	ER to Golgi Anterograde Transport
R-HSA-199991	Membrane Trafficking
R-HSA-373760	L1CAM interactions
R-HSA-392499	Metabolism of proteins
R-HSA-422475	Axon guidance
R-HSA-446203	Asparagine N-linked glycosylation
R-HSA-5653656	Vesicle-mediated transport
R-HSA-5683057	MAPK family signaling cascades
R-HSA-5684996	MAPK1/MAPK3 signaling
R-HSA-597592	Post-translational protein modification
R-HSA-948021	Transport to the Golgi and subsequent modification
R-HSA-9675108	Nervous system development

MSigDB gene sets: 104 (showing top): GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, GOBP_LYSOSOMAL_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_POLYMERIZATION, REACTOME_NCAM_SIGNALING_FOR_NEURITE_OUT_GROWTH, GOBP_VACUOLAR_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_ACTIN_FILAMENT_DEPOLYMERIZATION, REACTOME_MEMBRANE_TRAFFICKING, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_REGULATION_OF_ACTIN_FILAMENT_BASED_PROCESS, GOBP_REGULATION_OF_ANATOMICAL_STRUCTURE_SIZE, ACEVEDO_LIVER_TUMOR_VS_NORMAL_ADJACENT_TISSUE_DN, GOBP_ACTIN_FILAMENT_ORGANIZATION, GOBP_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY

GO Biological Process (4): Golgi organization (GO:0007030), lysosomal transport (GO:0007041), actin cytoskeleton organization (GO:0030036), actin filament capping (GO:0051693)

GO Molecular Function (11): opsin binding (GO:0002046), actin binding (GO:0003779), kinesin binding (GO:0019894), spectrin binding (GO:0030507), myosin tail binding (GO:0032029), dynactin binding (GO:0034452), identical protein binding (GO:0042802), dynein intermediate chain binding (GO:0045505), actin filament binding (GO:0051015), protein binding (GO:0005515), cytoskeletal protein binding (GO:0008092)

GO Cellular Component (16): cytoplasm (GO:0005737), cytosol (GO:0005829), microtubule associated complex (GO:0005875), plasma membrane (GO:0005886), spectrin (GO:0008091), membrane (GO:0016020), cell junction (GO:0030054), cortical actin cytoskeleton (GO:0030864), photoreceptor connecting cilium (GO:0032391), cell projection (GO:0042995), apical cortex (GO:0045179), photoreceptor disc membrane (GO:0097381), cytoskeleton (GO:0005856), cortical cytoskeleton (GO:0030863), organelle (GO:0043226), plasma membrane bounded cell projection (GO:0120025)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
Axon guidance	2
L1CAM interactions	1
MAPK1/MAPK3 signaling	1
ER to Golgi Anterograde Transport	1
Membrane Trafficking	1
Transport to the Golgi and subsequent modification	1
Vesicle-mediated transport	1
Nervous system development	1
Post-translational protein modification	1
Signal Transduction	1
MAPK family signaling cascades	1
Metabolism of proteins	1
Asparagine N-linked glycosylation	1
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
protein binding	4
cytoskeletal protein binding	4
protein-containing complex binding	2
protein-containing complex	2
organelle organization	1
endomembrane system organization	1
vacuolar transport	1
cytoskeleton organization	1
actin filament-based process	1
negative regulation of actin filament depolymerization	1
negative regulation of actin filament polymerization	1
myosin heavy chain binding	1
actin binding	1
binding	1
intracellular anatomical structure	1
cytoplasm	1
microtubule cytoskeleton	1
membrane	1
cell periphery	1
cortical actin cytoskeleton	1
actin cytoskeleton	1
cortical cytoskeleton	1
ciliary transition zone	1
photoreceptor cell cilium	1
cell cortex region	1
photoreceptor outer segment	1
organelle membrane	1
intracellular membraneless organelle	1
cytoskeleton	1
cell cortex	1
cell projection	1
plasma membrane region	1

Protein interactions and networks

STRING

716 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPTBN5	ANK1	P16157	886
SPTBN5	EPB41	P11171	830
SPTBN5	ANK2	Q01484	815
SPTBN5	ANK3	Q12955	797
SPTBN5	SPTA1	P02549	751
SPTBN5	SPTAN1	Q13813	747
SPTBN5	SLC4A1	P02730	531
SPTBN5	PLEK2	Q9NYT0	490
SPTBN5	PLEK	P08567	470
SPTBN5	DCTN2	Q13561	463
SPTBN5	CD5L	O43866	437
SPTBN5	SPTBN1	Q01082	422
SPTBN5	ADD2	P35612	377
SPTBN5	EPB42	P16452	369
SPTBN5	SORBS3	O60504	359

IntAct

15 interactions, top by confidence:

A	B	Type	Score
SPTBN5	SBDS	psi-mi:“MI:0915”(physical association)	0.540
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
P		psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
BMI1	MEIS3P1	psi-mi:“MI:0914”(association)	0.350
RYBP	FAM186A	psi-mi:“MI:0914”(association)	0.350
FBF1	OFD1	psi-mi:“MI:2364”(proximity)	0.270
CANX	NACA	psi-mi:“MI:2364”(proximity)	0.270
AGGF1	BLTP3B	psi-mi:“MI:2364”(proximity)	0.270
GPKOW	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
PPIL4	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
RPS11	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
SBDS	RPSA2	psi-mi:“MI:2364”(proximity)	0.270
DDX6	RPSA2	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (19): SPTBN5 (Co-fractionation), SPTBN5 (Synthetic Lethality), SPTBN5 (Proximity Label-MS), SPTBN5 (Affinity Capture-MS), SPTBN5 (Affinity Capture-MS), SPTBN5 (Proximity Label-MS), SPTBN5 (Protein-RNA), SPTBN5 (Affinity Capture-MS), SBDS (Proximity Label-MS), SPTBN5 (Proximity Label-MS), SPTBN5 (Proximity Label-MS), SPTBN5 (Proximity Label-MS), SPTBN5 (Affinity Capture-MS), SPTBN5 (Affinity Capture-MS), AARS (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A8M2BID5, A2CG49, D3ZEY0, D3ZHV2, E9Q557, E9Q8Q6, F1LMV6, F1M0Z1, G3V7L1, O15068, O60229, O60437, O75962, O97592, P02549, P10911, P11277, P11530, P11531, P11532, P11533, P15508, P15924, P30427, P46939, P97924, Q03001, Q0KL02, Q15149, Q1LUA6, Q4FZC9, Q5GN48, Q63406, Q64096, Q6ZMZ3, Q6ZP82, Q6ZWQ0, Q6ZWR6, Q86YR7, Q8NF91

Diamond homologs: A5D7D1, D3ZEN0, D3ZHA0, D3ZHV2, D3ZQL6, E1BBG2, F1MF74, F1RA39, F6QZ15, G3MWR8, G3V7L1, L7UZ85, M9MRD1, O13728, O15020, O43707, O75369, O76329, O88990, O94851, O97592, P05094, P05095, P07751, P11277, P11530, P11531, P11532, P11533, P12814, P13395, P13466, P15508, P16086, P16546, P18091, P20111, P21333, P30427, P35609

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	711
Likely benign	153
Benign	46

Top pathogenic / likely-pathogenic (0)

SpliceAI

10869 predictions. Top by Δscore:

Variant	Effect	Δscore
15:41848625:AGACC:A	acceptor_loss	1.0000
15:41848628:CCTG:C	acceptor_loss	1.0000
15:41848629:C:A	acceptor_loss	1.0000
15:41848629:C:CC	acceptor_gain	1.0000
15:41849955:CTGGG:C	acceptor_gain	1.0000
15:41849960:C:CC	acceptor_gain	1.0000
15:41851055:TCAC:T	donor_loss	1.0000
15:41851056:CACCT:C	donor_loss	1.0000
15:41851058:C:CT	donor_loss	1.0000
15:41851147:CTTT:C	acceptor_gain	1.0000
15:41851148:TTT:T	acceptor_gain	1.0000
15:41851149:TT:T	acceptor_gain	1.0000
15:41851149:TTCTG:T	acceptor_loss	1.0000
15:41851151:C:CA	acceptor_loss	1.0000
15:41851151:C:CC	acceptor_gain	1.0000
15:41851284:T:TA	donor_gain	1.0000
15:41851294:T:TA	donor_gain	1.0000
15:41851365:CTAGG:C	acceptor_gain	1.0000
15:41851366:TAGG:T	acceptor_gain	1.0000
15:41851370:C:CC	acceptor_gain	1.0000
15:41851774:CTCA:C	donor_loss	1.0000
15:41851776:CA:C	donor_loss	1.0000
15:41851778:C:CG	donor_loss	1.0000
15:41851849:TC:T	acceptor_gain	1.0000
15:41851850:CC:C	acceptor_gain	1.0000
15:41851851:C:CC	acceptor_gain	1.0000
15:41851857:A:C	acceptor_gain	1.0000
15:41852216:AGCC:A	donor_gain	1.0000
15:41852628:CGTCA:C	donor_loss	1.0000
15:41852631:CACCT:C	donor_loss	1.0000

AlphaMissense

23755 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:41887971:A:G	W206R	0.988
15:41887971:A:T	W206R	0.988
15:41893311:A:G	W63R	0.977
15:41893311:A:T	W63R	0.977
15:41887952:A:G	F212S	0.974
15:41887972:G:C	S205R	0.973
15:41887972:G:T	S205R	0.973
15:41887974:T:G	S205R	0.973
15:41890116:G:C	F158L	0.970
15:41890116:G:T	F158L	0.970
15:41890118:A:G	F158L	0.970
15:41887962:C:A	G209W	0.961
15:41893318:G:C	F60L	0.958
15:41893318:G:T	F60L	0.958
15:41893320:A:G	F60L	0.958
15:41887961:C:T	G209E	0.957
15:41887981:G:C	F202L	0.952
15:41887981:G:T	F202L	0.952
15:41887983:A:G	F202L	0.952
15:41893309:C:A	W63C	0.950
15:41893309:C:G	W63C	0.950
15:41887375:G:C	F242L	0.948
15:41887375:G:T	F242L	0.948
15:41887377:A:G	F242L	0.948
15:41887982:A:G	F202S	0.948
15:41892906:G:C	F124L	0.945
15:41892906:G:T	F124L	0.945
15:41892908:A:G	F124L	0.945
15:41887951:G:C	F212L	0.944
15:41887951:G:T	F212L	0.944

dbSNP variants (sampled 300 via entrez): RS1000006640 (15:41853323 G>A), RS1000192193 (15:41872764 G>T), RS1000375889 (15:41886841 G>C,T), RS1000427678 (15:41867175 G>A), RS1000458836 (15:41850457 C>T), RS1000538026 (15:41857555 C>T), RS1000552769 (15:41893646 G>T), RS1000609082 (15:41871660 C>A,T), RS1000610895 (15:41889293 T>A), RS1000693798 (15:41847808 T>G), RS1000774736 (15:41882514 G>A,T), RS1000991028 (15:41863119 G>A), RS1001023510 (15:41877320 T>A), RS1001056931 (15:41871881 C>T), RS1001247548 (15:41880318 G>A,T)

Disease associations

OMIM: gene MIM:605916 | disease phenotypes: MIM:209850

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Limited	Autosomal dominant

Mondo (2): autism (MONDO:0005260), neurodevelopmental disorder (MONDO:0700092)

Orphanet (0):

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0000717	Autism

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST007483_41	Waist-to-hip ratio adjusted for BMI (additive genetic model)	4.000000e-06
GCST007487_7	Waist-to-hip ratio adjusted for BMI (additive genetic model)	2.000000e-06
GCST007500_8	Waist-to-hip ratio adjusted for BMI (additive genetic model)	3.000000e-06
GCST008161_61	Waist circumference adjusted for body mass index	6.000000e-06
GCST90020025_126	Waist-to-hip ratio adjusted for BMI	2.000000e-08
GCST90020025_143	Waist-to-hip ratio adjusted for BMI	6.000000e-09
GCST90020027_630	Waist-hip index	4.000000e-08
GCST90020027_631	Waist-hip index	1.000000e-08
GCST90020029_290	Waist circumference adjusted for body mass index	1.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0007789	BMI-adjusted waist circumference

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression	2
Benzo(a)pyrene	affects methylation, decreases methylation	2
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
2,5,2’,5’-tetrachlorobiphenyl	decreases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
butyraldehyde	increases expression	1
abrine	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
prothioconazole	decreases expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Amphotericin B	increases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Estradiol	increases expression, affects cotreatment	1
Dronabinol	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	increases expression	1
Valproic Acid	increases methylation	1
Vitamin E	decreases expression	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

498 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,
NCT00211796	PHASE4	COMPLETED	Divalproex Sodium ER in Adult Autism
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT00409747	PHASE4	COMPLETED	Minocycline to Treat Childhood Regressive Autism
NCT00576732	PHASE4	COMPLETED	A Study of the Effectiveness and Safety of Two Doses of Risperidone in the Treatment of Children and Adolescents With Autistic Disorder
NCT00844753	PHASE4	COMPLETED	Atomoxetine, Placebo and Parent Management Training in Autism
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01098383	PHASE4	UNKNOWN	Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02069977	PHASE4	UNKNOWN	Study to Evaluate the Efficacy and Safety of Aripiprazole
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02199925	PHASE4	UNKNOWN	An Open-Label Study to Evaluate the Efficacy of High-Dose Gammaplex in Children on the Autism Spectrum
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02255565	PHASE4	COMPLETED	Dose Response Effects of Quillivant XR in Children With ADHD and Autism: A Pilot Study
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
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
NCT00036231	PHASE3	TERMINATED	Synthetic Human Secretin in Children With Autism and Gastrointestinal Dysfunction
NCT00036244	PHASE3	COMPLETED	Synthetic Human Secretin in Children With Autism
NCT00065884	PHASE3	UNKNOWN	Valproate Response in Aggressive Autistic Adolescents
NCT00065962	PHASE3	COMPLETED	Secretin for the Treatment of Autism
NCT00252603	PHASE3	COMPLETED	Galantamine Versus Placebo in Childhood Autism