ANKS1B

Summary

ANKS1B (ankyrin repeat and sterile alpha motif domain containing 1B, HGNC:24600) is a protein-coding gene on chromosome 12q23.1, encoding Ankyrin repeat and sterile alpha motif domain-containing protein 1B (Q7Z6G8). Isoform 2 may participate in the regulation of nucleoplasmic coilin protein interactions in neuronal and transformed cells.

This gene encodes a multi-domain protein that is predominantly expressed in brain and testis. This protein interacts with amyloid beta protein precursor (AbetaPP) and may have a role in normal brain development, and in the pathogenesis of Alzheimer’s disease. Expression of this gene has been shown to be elevated in patients with pre-B cell acute lymphocytic leukemia associated with t(1;19) translocation. Alternatively spliced transcript variants encoding different isoforms (some with different subcellular localization, PMID:15004329) have been described for this gene.

Source: NCBI Gene 56899 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Moderate, GenCC) — +1 more curated relationship
• GWAS associations: 24
• Clinical variants (ClinVar): 219 total — 3 pathogenic, 3 likely-pathogenic
• MANE Select transcript: NM_001352186

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24600
Approved symbol	ANKS1B
Name	ankyrin repeat and sterile alpha motif domain containing 1B
Location	12q23.1
Locus type	gene with protein product
Status	Approved
Aliases	EB-1, AIDA-1, cajalin-2, ANKS2
Ensembl gene	ENSG00000185046
Ensembl biotype	protein_coding
OMIM	607815
Entrez	56899

Gene structure

Transcript identifiers

Ensembl transcripts: 34 — 21 protein_coding, 10 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000333732, ENST00000341752, ENST00000546364, ENST00000546568, ENST00000546631, ENST00000546960, ENST00000547010, ENST00000547362, ENST00000547446, ENST00000547776, ENST00000548447, ENST00000549025, ENST00000549315, ENST00000549493, ENST00000549558, ENST00000549797, ENST00000549866, ENST00000550157, ENST00000550693, ENST00000550778, ENST00000550833, ENST00000551212, ENST00000551560, ENST00000551613, ENST00000551830, ENST00000552210, ENST00000552232, ENST00000552245, ENST00000552407, ENST00000552472, ENST00000552748, ENST00000555119, ENST00000557083, ENST00000683438

RefSeq mRNA: 52 — MANE Select: NM_001352186 NM_001204065, NM_001204066, NM_001204067, NM_001204068, NM_001204069, NM_001204070, NM_001204079, NM_001204080, NM_001204081, NM_001352185, NM_001352186, NM_001352187, NM_001352188, NM_001352189, NM_001352190, NM_001352191, NM_001352192, NM_001352193, NM_001352194, NM_001352195, NM_001352196, NM_001352197, NM_001352198, NM_001352199, NM_001352200, NM_001352201, NM_001352202, NM_001352203, NM_001352204, NM_001352205, NM_001352206, NM_001352207, NM_001352208, NM_001352209, NM_001352210, NM_001352211, NM_001352212, NM_001352213, NM_001352214, NM_001352216, NM_001352217, NM_001352218, NM_001352219, NM_001352220, NM_001352221, NM_001352222, NM_001352223, NM_001352224, NM_001352225, NM_020140, NM_152788, NM_181670

CCDS: CCDS55864, CCDS55865, CCDS55866, CCDS55867, CCDS55868, CCDS55869, CCDS55870, CCDS55871, CCDS55872, CCDS86326, CCDS91740

Canonical transcript exons

ENST00000683438 — 27 exons

Exon	Start	End
ENSE00001292657	99244342	99244414
ENSE00001293250	99399631	99399811
ENSE00001295894	99775548	99775661
ENSE00001311234	99772922	99773088
ENSE00001313584	99246275	99246864
ENSE00001314358	99504476	99504641
ENSE00001324154	99443673	99443809
ENSE00001367088	99806404	99806700
ENSE00001378981	99812155	99812311
ENSE00001388727	99782022	99782097
ENSE00001390742	99779871	99779972
ENSE00001391356	99825309	99825389
ENSE00002472870	98743974	98745849
ENSE00003315949	98782126	98782137
ENSE00003480275	98773042	98773179
ENSE00003493369	99655067	99655210
ENSE00003496614	99053157	99053309
ENSE00003506514	98751355	98751522
ENSE00003525903	99154289	99154395
ENSE00003554675	99084925	99085023
ENSE00003561791	98807844	98807918
ENSE00003563196	98832029	98832136
ENSE00003649773	98829174	98829353
ENSE00003657947	98800997	98801125
ENSE00003785847	98798934	98799005
ENSE00003786874	98781117	98781203
ENSE00003925771	99984104	99984936

Expression profiles

Bgee: expression breadth ubiquitous, 210 present calls, max score 98.78.

FANTOM5 (CAGE): breadth broad, TPM avg 11.3745 / max 803.8024, expressed in 642 samples.

FANTOM5 promoters (33 alternative TSS)

Promoter ID	TPM avg	Samples expressed
132849	3.4595	148
132862	1.8528	118
132861	1.3385	111
132880	1.0465	451
132878	0.6855	227
132848	0.5806	88
132856	0.4466	83
132857	0.3570	72
132876	0.2078	70
132860	0.2066	76

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
Brodmann (1909) area 23	UBERON:0013554	98.78	gold quality
inferior vagus X ganglion	UBERON:0005363	98.48	gold quality
primary visual cortex	UBERON:0002436	98.27	gold quality
endothelial cell	CL:0000115	98.05	gold quality
corpus callosum	UBERON:0002336	98.03	gold quality
middle temporal gyrus	UBERON:0002771	97.71	gold quality
subthalamic nucleus	UBERON:0001906	97.65	gold quality
ventral tegmental area	UBERON:0002691	97.49	gold quality
entorhinal cortex	UBERON:0002728	97.45	gold quality
parietal lobe	UBERON:0001872	97.34	gold quality
postcentral gyrus	UBERON:0002581	97.14	gold quality
lateral nuclear group of thalamus	UBERON:0002736	96.88	gold quality
medial globus pallidus	UBERON:0002477	96.87	gold quality
globus pallidus	UBERON:0001875	96.86	gold quality
occipital lobe	UBERON:0002021	96.86	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.86	gold quality
superior vestibular nucleus	UBERON:0007227	96.69	gold quality
nucleus accumbens	UBERON:0001882	96.68	gold quality
prefrontal cortex	UBERON:0000451	96.63	gold quality
superior frontal gyrus	UBERON:0002661	96.43	gold quality
spinal cord	UBERON:0002240	96.15	gold quality
pons	UBERON:0000988	95.99	gold quality
lateral globus pallidus	UBERON:0002476	95.94	gold quality
temporal lobe	UBERON:0001871	95.78	gold quality
caudate nucleus	UBERON:0001873	95.75	gold quality
Ammon’s horn	UBERON:0001954	95.60	gold quality
cortical plate	UBERON:0005343	95.44	gold quality
frontal cortex	UBERON:0001870	95.14	gold quality
neocortex	UBERON:0001950	95.05	gold quality
substantia nigra pars reticulata	UBERON:0001966	94.94	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	58.19
E-ANND-3	yes	6.39
E-MTAB-10137	no	56.57
E-MTAB-6386	no	39.31
E-MTAB-6142	no	37.93

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

68 targeting ANKS1B, 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-340-5P	100.00	72.50	4437
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-34B-5P	99.78	67.56	1175
HSA-MIR-449C-5P	99.78	67.63	1168
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-623	99.76	68.16	1170
HSA-MIR-2682-5P	99.73	67.38	1055
HSA-MIR-6505-5P	99.73	69.25	1595
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306

Literature-anchored findings (GeneRIF, showing 20)

• site-specific translocation and evidence of postnatal origin of the t(1;19) fusion in childhood acute lymphoblastic leukemia (PMID:12415113)
• Evidence pertaining to leukemogenesis by the well-characterized E2A-fusion protein E2A-PBX1 is reviewed and its mechanistic implications are considered. (PMID:12700034)
• Amyloid beta-protein precursor expression and secretion are regulated via activation of ERK1/2 by HGF in cells transfected with APP751. (PMID:12837293)
• AbetaPP and the AIDA-1 proteins interact in vitro, in living cells and, endogenously, in leukemia cell lines;AIDA-1 proteins are expressed at high levels in the brain (PMID:15004329)
• the interaction between AbetaPP and AIDA-1 is regulated by alternative splicing of the AIDA-1 protein (PMID:15347684)
• specific EB-1/AIDA-1 isoforms, such as AIDA-1c, may participate in the regulation of nucleoplasmic coilin protein interactions in neuronal and transformed cells (PMID:15862129)
• The TCR gene rearrangements in childhood B-lineage acute lymphoblastic leukemia was associated with expression of E2A-Pbx1 fusion protein chimeric oncogene. (PMID:16386788)
• Targeted-E2A-PBX1 inhibition leads to reduced expression of the EB-1 and Wnt16b genes; aberrant expression of these genes may be a key step in leukemogenesis in t(1;19)-positive pre-B leukemia. (PMID:16769578)
• The basic nuclear import signal for AIDA-1 is buried at the interface between the two sterile alpha motif domains. (PMID:19666031)
• EB1 recognizes the nucleotide state of tubulin in the microtubule lattice (PMID:19851462)
• It is clear that some single-nucleotide polymorphisms and haplotypes of the EB-1 gene are associated with genetic difference between diabetic patients with and without nephropathy. (PMID:20578947)
• AIDA1 PTB domain binds amyloid protein precursorin a similar manner to the X11/Mint PTB domain. (PMID:23799029)
• We provide the first evidence that ANKS1B expression is down regulated in ccRCC tumors relative to patient-matched normal kidney tissue in smokers. (PMID:24479813)
• this is the first genetic association study of the relationship between the rs7968606 SNP of ANKS1B and the response of schizophrenia patients to treatment with amisulpride. (PMID:28332719)
• Our data uncover an essential role of the novel circular RNA circANKS1B in the metastasis of breast cancer, which demonstrate that therapeutic targeting of circANKS1B may better prevent breast cancer metastasis. (PMID:30454010)
• Study describe monogenic copy-number variations in ANKS1B in individuals that display a previously undefined spectrum of neurodevelopmental phenotypes that authors term ANKS1B haploinsufficiency syndrome. (PMID:31388001)
• Circular RNA circANKS1B acts as a sponge for miR-152-3p and promotes prostate cancer progression by upregulating TGF-alpha expression. (PMID:33556191)
• Regulation of transforming growth factor-beta1 by circANKS1B/miR-515-5p affects the metastatic potential and cisplatin resistance in oral squamous cell carcinoma. (PMID:34781814)
• Replication stress causes delayed mitotic entry and chromosome 12 fragility at the ANKS1B large neuronal gene in human induced pluripotent stem cells. (PMID:37597021)
• AIDA-1/ANKS1B Binds to the SynGAP Family RasGAPs with High Affinity and Specificity. (PMID:38759928)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	anks1b	ENSDARG00000003512
mus_musculus	Anks1b	ENSMUSG00000058589
rattus_norvegicus	Anks1b	ENSRNOG00000024870

Paralogs (1): ANKS1A (ENSG00000064999)

Protein

Protein identifiers

Ankyrin repeat and sterile alpha motif domain-containing protein 1B — Q7Z6G8 (reviewed: Q7Z6G8)

Alternative names: Amyloid-beta protein intracellular domain-associated protein 1, E2A-PBX1-associated protein

All UniProt accessions (14): Q7Z6G8, A0A804HKX1, F8VR14, F8VVQ4, H0YI72, H0YJZ1, R4GMN5, R4GMQ4, R4GMS8, R4GN07, R4GN70, R4GN73, R4GN78, R4GNJ0

UniProt curated annotations — full annotation on UniProt →

Function. Isoform 2 may participate in the regulation of nucleoplasmic coilin protein interactions in neuronal and transformed cells. Isoform 3 can regulate global protein synthesis by altering nucleolar numbers. Isoform 4 may play a role as a modulator of APP processing. Overexpression can down-regulate APP processing.

Subunit / interactions. Isoform 3 interacts with DLG4. Interacts with EPHA8. Isoform 2 interacts with COIL. Isoform 4 interacts with APP and EPHA8. Isoform 6 interacts with EPHA8.

Subcellular location. Cytoplasm Nucleus Postsynaptic density. Cell projection. Dendritic spine. Nucleus. Cajal body Nucleus Nucleus.

Tissue specificity. Highly expressed in marrow from patients with pre-B ALL associated with the t(1;19) translocation. Strongly expressed in brain and testis. Expressed in fetal brain. Isoform 4 is highly expressed in brain (at protein level). Isoform 6 is expressed in brain and several cancer cell lines.

Post-translational modifications. Isoform 3 nuclear translocation requires an NMDAR-dependent proteolytic cleavage.

Induction. Transcriptionally up-regulated in t(1:19) pre-B cell acute lymphocytic leukemia by the chimeric TCF3-PBX1. Not expressed in pre-B cell that lack this translocation.

Isoforms (10)

UniProt ID	Names	Canonical?
Q7Z6G8-1	1, AIDA-1b	yes
Q7Z6G8-2	2, AIDA-1c
Q7Z6G8-3	3
Q7Z6G8-4	4, AIDA-1a
Q7Z6G8-5	5
Q7Z6G8-6	6, AIDA-1bDeltaAnk
Q7Z6G8-7	7
Q7Z6G8-8	8
Q7Z6G8-9	9
Q7Z6G8-10	10

RefSeq proteins (52): NP_001190994, NP_001190995, NP_001190996, NP_001190997, NP_001190998, NP_001190999, NP_001191008, NP_001191009, NP_001191010, NP_001339114, NP_001339115, NP_001339116, NP_001339117, NP_001339118, NP_001339119, NP_001339120, NP_001339121, NP_001339122, NP_001339123, NP_001339124, NP_001339125, NP_001339126, NP_001339127, NP_001339128, NP_001339129, NP_001339130, NP_001339131, NP_001339132, NP_001339133, NP_001339134, NP_001339135, NP_001339136, NP_001339137, NP_001339138, NP_001339139, NP_001339140, NP_001339141, NP_001339142, NP_001339143, NP_001339145, NP_001339146, NP_001339147, NP_001339148, NP_001339149, NP_001339150, NP_001339151, NP_001339152, NP_001339153, NP_001339154, NP_064525, NP_690001, NP_858056 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001660	SAM	Domain
IPR002110	Ankyrin_rpt	Repeat
IPR006020	PTB/PI_dom	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR013761	SAM/pointed_sf	Homologous_superfamily
IPR033635	ANKS1/Caskin	Family
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily
IPR041880	SAM_ANKS1_repeat1	Domain
IPR041882	SAM_ANKS1_repeat2	Domain

Pfam: PF00536, PF00640, PF12796

UniProt features (88 total): modified residue 14, splice variant 14, helix 13, strand 9, compositionally biased region 8, repeat 7, region of interest 7, sequence conflict 6, turn 5, domain 3, chain 1, short sequence motif 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
2EAM	SOLUTION NMR
2KE7	SOLUTION NMR
2KIV	SOLUTION NMR
2M38	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z6G8-F1	57.16	0.18

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 (14): 309, 310, 314, 353, 364, 503, 507, 510, 738, 773, 775, 901, 974, 1007

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 222 (showing top): GCM_MAP4K4, GCM_PTPRD, GGGTGGRR_PAX4_03, PAX2_01, GTGCCTT_MIR506, TCF4_Q5, GATA3_01, BRN2_01, OCT1_03, GATA6_01, TGIF_01, HFH4_01, E4F1_Q6, GOBP_EPHRIN_RECEPTOR_SIGNALING_PATHWAY, TGACATY_UNKNOWN

GO Biological Process (1): ephrin receptor signaling pathway (GO:0048013)

GO Molecular Function (2): ephrin receptor binding (GO:0046875), protein binding (GO:0005515)

GO Cellular Component (11): nucleoplasm (GO:0005654), centrosome (GO:0005813), cytosol (GO:0005829), plasma membrane (GO:0005886), postsynaptic density (GO:0014069), Cajal body (GO:0015030), dendritic spine (GO:0043197), nucleus (GO:0005634), cytoplasm (GO:0005737), cell projection (GO:0042995), synapse (GO:0045202)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cell surface receptor protein tyrosine kinase signaling pathway	1
signaling receptor binding	1
binding	1
nuclear lumen	1
centriole	1
microtubule organizing center	1
cytoplasm	1
membrane	1
cell periphery	1
asymmetric synapse	1
postsynaptic specialization	1
nuclear ribonucleoprotein granule	1
dendrite	1
neuron spine	1
postsynapse	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cell junction	1

Protein interactions and networks

STRING

2382 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ANKS1B	APP	P05067	554
ANKS1B	EPHA1	P21709	547
ANKS1B	PBX1	P40424	510
ANKS1B	RIN1	Q13671	508
ANKS1B	CNTNAP5	Q8WYK1	477
ANKS1B	CAMK2B	Q13554	476
ANKS1B	CAMK2A	Q9UQM7	466
ANKS1B	DLGAP1	P78335	462
ANKS1B	TCF3	P15883	459
ANKS1B	EPHA2	P29317	459
ANKS1B	KRIT1	O00522	448
ANKS1B	EGFLAM	Q63HQ2	437
ANKS1B	ADAM30	Q9UKF2	429
ANKS1B	MYOZ3	Q8TDC0	428
ANKS1B	PHACTR1	Q9C0D0	427

IntAct

16 interactions, top by confidence:

A	B	Type	Score
ANKS1B	EGFR	psi-mi:“MI:0407”(direct interaction)	0.440
ANKS1B	ERBB2	psi-mi:“MI:0407”(direct interaction)	0.440
ANKS1B	ERBB4	psi-mi:“MI:0407”(direct interaction)	0.440
ITGB7	ANKS1B	psi-mi:“MI:0407”(direct interaction)	0.440
ITGB3	ANKS1B	psi-mi:“MI:0407”(direct interaction)	0.440
ANKS1B	ITGB1	psi-mi:“MI:0407”(direct interaction)	0.440
HTR2A	ANKS1B	psi-mi:“MI:0915”(physical association)	0.370
SHC1	KDM1A	psi-mi:“MI:0914”(association)	0.350
SCRIB	CHD2	psi-mi:“MI:0914”(association)	0.350
ANKS1B	MCC	psi-mi:“MI:0914”(association)	0.350
CD2AP	ANKS1B	psi-mi:“MI:0915”(physical association)	0.000
APP	ANKS1B	psi-mi:“MI:0915”(physical association)	0.000
CASS4	ANKS1B	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (30): EPHA8 (Affinity Capture-Western), ANKS1B (Two-hybrid), ANKS1B (Affinity Capture-RNA), ANKS1B (Two-hybrid), ANKS1B (Two-hybrid), ANKS1B (Two-hybrid), ANKS1B (Two-hybrid), ANKS1B (Two-hybrid), ANKS1B (Affinity Capture-MS), ANKS1B (Two-hybrid), ANKS1B (Affinity Capture-MS), ANKS1B (Two-hybrid), MCC (Affinity Capture-MS), RASAL2 (Affinity Capture-MS), RIN2 (Affinity Capture-MS)

ESM2 similar proteins: A1A5G2, A2AFR3, A7MBL8, B9EJ86, E1C1R4, E1C3P4, F1LXF1, O94806, O94967, P0C6S7, P0CAX5, P11274, P22682, Q0V9G5, Q14161, Q14CM0, Q15139, Q16513, Q1RMU2, Q3KR37, Q3LAC4, Q3UGM2, Q5RED8, Q5T6S3, Q5U252, Q62101, Q66H62, Q6DFZ1, Q6P5G6, Q6PAJ1, Q70Z35, Q7Z6G8, Q80TI0, Q80TQ2, Q80YA9, Q8BIZ1, Q8BWW9, Q8BY87, Q8K1Y2, Q8NEL9

Diamond homologs: A0A8I3NFE2, A5PMU4, D3ZAR1, O09127, O15357, O70143, P0C6S7, P29321, P29353, P54753, P54754, P54755, P54756, P54758, P59672, P98083, Q03145, Q07498, Q09YL6, Q0IIE2, Q2I6J1, Q32PV0, Q3V1H9, Q5M824, Q5PQS4, Q5R7W7, Q5SW96, Q5TGI4, Q60629, Q61120, Q62413, Q6DD51, Q6P549, Q6P9K8, Q6S5L9, Q7Z6G8, Q801G1, Q8BIZ1, Q8C142, Q8K2A1

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
ANKS1B	up-regulates	“Postsynaptic density assembly”
ANKS1B	“up-regulates activity”	DLG4	binding
CAMK2A	“down-regulates activity”	ANKS1B	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 15 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
RAF/MAP kinase cascade	5	23.5×	4e-05
Hemostasis	5	13.9×	3e-04

GO biological processes:

GO term	Partners	Fold	FDR
cell-cell adhesion	5	33.8×	5e-05
positive regulation of ERK1 and ERK2 cascade	5	28.4×	6e-05
cell migration	6	24.6×	3e-05
cell adhesion	5	12.5×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	3
Uncertain significance	150
Likely benign	21
Benign	11

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
3244442	NC_000012.11:g.(?100091767)(100270969_?)del	Pathogenic
3244443	NC_000012.11:g.(?100041953)(100219167_?)del	Pathogenic
4820048	NC_000012.12:g.99320672_99425960del	Pathogenic
1012626	GRCh37/hg19 12q23.1(chr12:100166700-100175875)x3	Likely pathogenic
1067469	NM_001352186.2(ANKS1B):c.3441+2T>C	Likely pathogenic
1176615	GRCh37/hg19 12q23.1(chr12:100166700-100175875)x1	Likely pathogenic

SpliceAI

4810 predictions. Top by Δscore:

Variant	Effect	Δscore
12:98727317:G:GC	donor_loss	1.0000
12:98727318:T:G	donor_loss	1.0000
12:98732418:A:AG	acceptor_gain	1.0000
12:98732418:AGT:A	acceptor_gain	1.0000
12:98732419:G:GG	acceptor_gain	1.0000
12:98732419:GTG:G	acceptor_gain	1.0000
12:98773033:GGTAC:G	donor_loss	1.0000
12:98773034:GTACT:G	donor_loss	1.0000
12:98773035:TACT:T	donor_loss	1.0000
12:98773036:ACT:A	donor_loss	1.0000
12:98773037:CT:C	donor_loss	1.0000
12:98773038:TCACC:T	donor_loss	1.0000
12:98773039:C:CG	donor_loss	1.0000
12:98773040:A:AC	donor_gain	1.0000
12:98773041:C:CC	donor_gain	1.0000
12:98773041:CCA:C	donor_gain	1.0000
12:98773176:TGTT:T	acceptor_gain	1.0000
12:98773178:TT:T	acceptor_gain	1.0000
12:98773179:TCT:T	acceptor_loss	1.0000
12:98781112:CTTA:C	donor_loss	1.0000
12:98781113:TTAC:T	donor_loss	1.0000
12:98781114:TACC:T	donor_loss	1.0000
12:98781116:C:G	donor_loss	1.0000
12:98781201:CTT:C	acceptor_gain	1.0000
12:98781204:C:CC	acceptor_gain	1.0000
12:98832027:AC:A	donor_gain	1.0000
12:98832028:CC:C	donor_gain	1.0000
12:99053153:TTAC:T	donor_loss	1.0000
12:99053154:TA:T	donor_loss	1.0000
12:99053155:A:AC	donor_gain	1.0000

AlphaMissense

8444 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:98751458:A:G	L1190P	1.000
12:98751462:C:G	A1189P	1.000
12:98751464:A:G	L1188P	1.000
12:98751467:T:G	Q1187P	1.000
12:98751471:A:C	Y1186D	1.000
12:98751473:G:T	A1185D	1.000
12:98751474:C:G	A1185P	1.000
12:98751479:T:A	E1183V	1.000
12:98751481:G:C	F1182L	1.000
12:98751481:G:T	F1182L	1.000
12:98751482:A:C	F1182C	1.000
12:98751482:A:G	F1182S	1.000
12:98751483:A:G	F1182L	1.000
12:98751483:A:T	F1182I	1.000
12:98751486:C:G	A1181P	1.000
12:98751491:C:A	G1179V	1.000
12:98751491:C:T	G1179E	1.000
12:98751492:C:G	G1179R	1.000
12:98751492:C:T	G1179R	1.000
12:98751494:A:G	L1178P	1.000
12:98751500:A:G	L1176P	1.000
12:98751509:T:A	E1173V	1.000
12:98773057:A:C	F1163L	1.000
12:98773057:A:T	F1163L	1.000
12:98773058:A:G	F1163S	1.000
12:98773059:A:G	F1163L	1.000
12:98773066:A:C	C1160W	1.000
12:98773067:C:T	C1160Y	1.000
12:98773068:A:G	C1160R	1.000
12:98773104:A:C	Y1148D	1.000

dbSNP variants (sampled 300 via entrez): RS1000000090 (12:98928447 A>G), RS1000000621 (12:99858513 C>T), RS1000002292 (12:99264440 C>T), RS1000004165 (12:98979039 G>A), RS1000004655 (12:99914536 T>A), RS1000008794 (12:99371877 C>T), RS1000011691 (12:99521770 G>C), RS1000013684 (12:99949479 C>G,T), RS1000016710 (12:98790053 A>G), RS1000017072 (12:99899167 A>G), RS1000017404 (12:99944131 G>A), RS1000018973 (12:98760163 CTTTA>C), RS1000022369 (12:99812597 T>A,C), RS1000022549 (12:98802723 T>G), RS1000027091 (12:99128816 G>A)

Disease associations

OMIM: gene MIM:607815 | disease phenotypes: MIM:192350

GenCC curated gene-disease

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Moderate	Autosomal dominant
neurodevelopmental disorder	Limited	Autosomal dominant

Mondo (5): primary ovarian failure (MONDO:0005387), VACTERL/vater association (MONDO:0008642), male infertility (MONDO:0005372), complex neurodevelopmental disorder (MONDO:0100038), neurodevelopmental disorder (MONDO:0700092)

Orphanet (2): VACTERL/VATER association (Orphanet:887), NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619)

HPO phenotypes

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

GWAS associations

24 associations (top):

Study	Trait	p-value
GCST000473_9	Response to antipsychotic treatment	3.000000e-07
GCST000838_3	Waist circumference	2.000000e-06
GCST000840_6	Body mass index	9.000000e-06
GCST000883_5	Response to antipsychotic treatment in schizophrenia (working memory)	4.000000e-07
GCST001663_13	Amyotrophic lateral sclerosis (age of onset)	8.000000e-06
GCST001762_643	Obesity-related traits	7.000000e-06
GCST001818_9	Metabolite levels (HVA/5-HIAA ratio)	3.000000e-06
GCST001877_70	Autism spectrum disorder, attention deficit-hyperactivity disorder, bipolar disorder, major depressive disorder, and schizophrenia (combined)	2.000000e-06
GCST002408_10	Response to methotrexate in juvenile idiopathic arthritis	5.000000e-06
GCST002706_5	Electrodermal activity	1.000000e-07
GCST004029_24	Angiotensin-converting enzyme inhibitor intolerance	3.000000e-07
GCST005926_4	Peak cortisol response to low dose short synacthen test in corticosteroid treated asthma	9.000000e-09
GCST006430_4	Body mass index and waist-hip ratio (pleiotropy)	1.000000e-06
GCST008103_131	Bipolar disorder	2.000000e-06
GCST008103_48	Bipolar disorder	2.000000e-07
GCST008115_46	Bipolar I disorder	5.000000e-07
GCST008645_1	Alcohol dependence or heroin dependence or methamphetamine dependence	4.000000e-09
GCST009531_1	Body fat percentage	3.000000e-08
GCST009600_95	Anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, or Tourette syndrome (pleiotropy)	1.000000e-08
GCST010313_10	Serum polyunsaturated fatty acid concentration x sex interaction in metabolic syndrome	9.000000e-06
GCST010988_499	Adult body size	2.000000e-11
GCST010989_47	Body size at age 10	6.000000e-10
GCST90013421_11	Left-handedness	2.000000e-11
GCST90020028_1674	Hip circumference adjusted for BMI	4.000000e-11

EFO canonical traits (16, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004335	short-term memory
EFO:0004847	age at onset
EFO:0005131	HVA measurement
EFO:0005132	5-HIAA measurement
EFO:0005325	response to angiotensin-converting enzyme inhibitor
EFO:0005843	cortisol measurement
EFO:0009175	response to synacthen
EFO:0004343	waist-hip ratio
EFO:0009963	bipolar I disorder
EFO:0007800	body fat percentage
EFO:0008343	sex interaction measurement
EFO:0010733	polyunsaturated fatty acid measurement
EFO:0009819	comparative body size at age 10, self-reported
EFO:0009902	handedness
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D007248	Infertility, Male	C12.100.500.430; C12.100.750.700; C12.200.294.430
D065886	Neurodevelopmental Disorders	F03.625
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

4 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs2133896	Toxicity	3	ethanol	Alcohol abuse
rs2133896	Toxicity	3	heroin	Heroin Dependence
rs2133896	Toxicity	3	methamphetamine	Methamphetamine dependence
rs7968606	Efficacy	3	amisulpride	Schizophrenia

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs7968606	ANKS1B	3	2.00	1	amisulpride
rs17028658	ANKS1B		0.00	0
rs2133896	ANKS1B	3	2.50	3	ethanol;heroin;methamphetamine

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, decreases expression	3
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	3
bisphenol A	decreases methylation, increases expression	2
entinostat	decreases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	decreases expression, increases methylation	2
Aflatoxin B1	decreases expression, decreases methylation	2
aristolochic acid I	decreases expression	1
bisphenol F	affects cotreatment, increases methylation	1
methyleugenol	decreases expression	1
butyraldehyde	decreases expression	1
perfluorooctanoic acid	decreases expression	1
aflatoxin B2	increases methylation	1
pentanal	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	1
perfluorohexanesulfonic acid	decreases expression	1
belinostat	decreases expression, affects cotreatment	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression, increases expression	1
jinfukang	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Panobinostat	affects cotreatment, decreases expression	1
Arsenic	affects methylation	1
Cisplatin	affects cotreatment, increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Ivermectin	increases expression	1

Clinical trials (associated diseases)

404 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,
NCT00417066	PHASE4	COMPLETED	Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders
NCT00732693	PHASE4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00837616	PHASE4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01853501	PHASE4	UNKNOWN	Effects of ADSC Therapy in Women With POF
NCT02783937	PHASE4	COMPLETED	Filgrastim for Premature Ovarian Insufficiency
NCT03535480	PHASE4	UNKNOWN	Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
NCT02202382	PHASE4	COMPLETED	Effects of Korean Red Ginseng on Male Infertility
NCT02204826	PHASE4	COMPLETED	Effects of Korean Red Ginseng on Semen Parameters in Male Infertility Patients: a Randomized, Placebo-controlled, Double-blind Clinical Study
NCT03802864	PHASE4	COMPLETED	Post-operative Pain Control of Testicular Sperm Extraction Using Liposomal Bupivacaine
NCT06100432	PHASE4	ACTIVE_NOT_RECRUITING	Effect of Eurycoma Longifolia (DLBS5055) and Multivitamins (Vitamin C+Vitamin E+ β-carotene) for Infertile Males
NCT07523022	PHASE4	ENROLLING_BY_INVITATION	Comparison of the Effect of Gonadotropin and Clomiphene Citrate Treatment on Sperm Parameters and the Outcome of Assisted Reproductive Procedures in Subfertile Men Based on the APHRODITE Groups
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
NCT00140998	PHASE3	COMPLETED	Estrogen Treatment (Oral vs. Patches) in Turner Syndrome
NCT00975117	PHASE3	COMPLETED	Spermotrend in the Treatment of Male Infertility
NCT01407432	PHASE3	COMPLETED	Impact of Folates in the Care of the Male Infertility
NCT01895816	PHASE3	COMPLETED	Herbal Tonic Fertile Supplement(ZO2C5)
NCT02605070	PHASE3	TERMINATED	Pilot Study on the Effects of FSH Treatment on the Epigenetic Characteristics of Spermatozoa in Infertile Patients With Severe Oligozoospermia
NCT07402759	PHASE3	ACTIVE_NOT_RECRUITING	Impact of tdrd9 Gene Mutations in the Therapeutic Response to L-carnitine in Oligoasthenozoospermic Men
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00001951	PHASE2	COMPLETED	Hormone Replacement in Young Women With Premature Ovarian Failure
NCT00370019	PHASE2	WITHDRAWN	Effects of an Estrogen Replacement Therapy Skin Patch on Ovulation in Women With Premature Ovarian Failure
NCT00429494	PHASE2	COMPLETED	GnRH Analogue for Ovarian Function Preservation in Hematopoietic Stem Cell Transplantation Patients
NCT03816852	PHASE2	SUSPENDED	The Safety and Efficiency Study of Mesenchymal Stem Cell (19#iSCLife®-POI) in Premature Ovarian Insufficiency
NCT04536467	PHASE2	UNKNOWN	Prevention of Chemotherapy-Induced Ovarian Failure With Goserelin in Premenopausal Lymphoma Patients
NCT06117982	PHASE2	COMPLETED	The Impact of Granulocyte Colony Stimulating Factor on Premature Ovarian Insufficiency
NCT01880086	PHASE2	COMPLETED	Clomiphene Citrate for the Treatment of Low Testosterone Associated With Chronic Opioid Pain Medication Administration
NCT02061384	PHASE2	COMPLETED	RA-2 13-cis Retinoic Acid (Isotretinoin)
NCT02421887	PHASE2	COMPLETED	Males, Antioxidants, and Infertility Trial
NCT05200663	PHASE2	UNKNOWN	Efficacy Comparison of Tamoxifen and Tamoxifen With Antioxidants on Semen Quality of Male With Idiopathic Infertility
NCT05290558	PHASE2	ACTIVE_NOT_RECRUITING	The Therapeutic Effects of Bu Shen Yi Jing Pill on Semen Quality in Sub Fertile Males: a Randomized Controlled Trial
NCT06091969	PHASE2	NOT_YET_RECRUITING	Supplementation for Male Subfertility
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants