CAMSAP2

Summary

CAMSAP2 (calmodulin regulated spectrin associated protein family member 2, HGNC:29188) is a protein-coding gene on chromosome 1q32.1, encoding Calmodulin-regulated spectrin-associated protein 2 (Q08AD1). Key microtubule-organizing protein that specifically binds the minus-end of non-centrosomal microtubules and regulates their dynamics and organization.

Enables microtubule minus-end binding activity. Involved in several processes, including axon development; regulation of dendrite development; and regulation of organelle organization. Located in Golgi apparatus; cytosol; and microtubule cytoskeleton.

Source: NCBI Gene 23271 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 180 total
• MANE Select transcript: NM_203459

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29188
Approved symbol	CAMSAP2
Name	calmodulin regulated spectrin associated protein family member 2
Location	1q32.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1078
Ensembl gene	ENSG00000118200
Ensembl biotype	protein_coding
OMIM	613775
Entrez	23271

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 5 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000236925, ENST00000358823, ENST00000413307, ENST00000447701, ENST00000475326, ENST00000532732, ENST00000924772

RefSeq mRNA: 4 — MANE Select: NM_203459 NM_001297707, NM_001297708, NM_001389638, NM_203459

CCDS: CCDS1404, CCDS72998, CCDS72999

Canonical transcript exons

ENST00000358823 — 17 exons

Exon	Start	End
ENSE00000796432	200848032	200850234
ENSE00000796434	200853275	200853495
ENSE00000796435	200854817	200854889
ENSE00000796436	200856010	200856125
ENSE00000796437	200857306	200857424
ENSE00001194133	200847640	200847709
ENSE00002165718	200857754	200860704
ENSE00002238336	200844782	200844869
ENSE00002248396	200807376	200807537
ENSE00002250815	200847210	200847292
ENSE00002266145	200760839	200761098
ENSE00002270890	200738893	200739966
ENSE00002283656	200832706	200832845
ENSE00002287717	200841994	200842087
ENSE00002294548	200815561	200815644
ENSE00002302184	200832200	200832341
ENSE00003656816	200852541	200852677

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 98.41.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.4642 / max 57.1017, expressed in 1374 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
7657	2.7734	1259
7656	0.6908	413

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lateral nuclear group of thalamus	UBERON:0002736	98.41	gold quality
postcentral gyrus	UBERON:0002581	98.39	gold quality
parietal lobe	UBERON:0001872	98.17	gold quality
cranial nerve II	UBERON:0000941	98.15	gold quality
endothelial cell	CL:0000115	98.00	gold quality
middle temporal gyrus	UBERON:0002771	97.55	gold quality
superior frontal gyrus	UBERON:0002661	97.54	gold quality
entorhinal cortex	UBERON:0002728	97.54	gold quality
Brodmann (1909) area 23	UBERON:0013554	97.47	gold quality
Brodmann (1909) area 46	UBERON:0006483	97.38	gold quality
lateral globus pallidus	UBERON:0002476	97.27	gold quality
CA1 field of hippocampus	UBERON:0003881	97.27	gold quality
substantia nigra pars compacta	UBERON:0001965	97.17	gold quality
medial globus pallidus	UBERON:0002477	97.06	gold quality
globus pallidus	UBERON:0001875	97.00	gold quality
superior vestibular nucleus	UBERON:0007227	96.97	gold quality
orbitofrontal cortex	UBERON:0004167	96.84	gold quality
substantia nigra pars reticulata	UBERON:0001966	96.81	gold quality
frontal pole	UBERON:0002795	96.68	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	96.65	gold quality
Brodmann (1909) area 10	UBERON:0013541	96.57	gold quality
medulla oblongata	UBERON:0001896	96.50	gold quality
cortical plate	UBERON:0005343	96.49	gold quality
pons	UBERON:0000988	96.25	gold quality
paraflocculus	UBERON:0005351	96.02	gold quality
ventral tegmental area	UBERON:0002691	95.90	gold quality
dorsal root ganglion	UBERON:0000044	95.68	gold quality
middle frontal gyrus	UBERON:0002702	95.54	gold quality
subthalamic nucleus	UBERON:0001906	95.38	gold quality
inferior olivary complex	UBERON:0002127	95.37	gold quality

Single-cell (SCXA)

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

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

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

254 targeting CAMSAP2, 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-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-3658	99.96	73.87	4379

Literature-anchored findings (GeneRIF, showing 13)

• The CKK domain binds microtubules and represents a domain that evolved with the metazoa. (PMID:19508979)
• in a two-stage GWAS to identify common susceptibility variants of epilepsy in Chinese, the strongest signals were observed with two highly correlated variants, rs2292096 and rs6660197, with the former reaching genome-wide significance, on 1q32.1 in the CAMSAP1L gene (PMID:22116939)
• the rs2292096 G allele of CAMSAP1L1, which was associated with reduced risk of symptomatic epilepsy, tended to associate with increased expression of CAMSAP1L1, which represses neurite outgrowth. (PMID:24148305)
• These results show that members of the CAMSAP/Patronin family all localize to and protect minus-ends but have evolved distinct effects on microtubule dynamics. (PMID:24706919)
• The CAMSAP/Nezha/Patronin family protein CAMSAP2 specifically localizes to noncentrosomal microtubule minus-ends and is required for proper microtubule organization in neurons. (PMID:24908486)
• noncentrosomal MTs regulate autophagy through a cross-talk between CAMSAP2 and EB1 (PMID:28726242)
• Microtubule Minus-End Binding Protein CAMSAP2 and Kinesin-14 Motor KIFC3 Control Dendritic Microtubule Organization. (PMID:32084403)
• CAMSAP2-mediated noncentrosomal microtubule acetylation drives hepatocellular carcinoma metastasis. (PMID:32206120)
• A chemical genetics approach to examine the functions of AAA proteins. (PMID:33782614)
• CircRNA SOD2 motivates non-small cell lungs cancer advancement with EMT via acting as microRNA-2355-5p’s competing endogenous RNA to mediate calmodulin regulated spectrin associated proteins-2. (PMID:35188072)
• CAMSAP2 and CAMSAP3 localize at microtubule intersections to regulate the spatial distribution of microtubules. (PMID:37567766)
• [High expression of CAMSAP2 promotes invasion and metastasis of gastric cancer cells by upregulating TGF-beta signaling]. (PMID:37814859)
• CAMSAP2 enhances lung cancer cell metastasis by mediating RASAL2 degradation. (PMID:38159595)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	camsap2a	ENSDARG00000062173
mus_musculus	Camsap2	ENSMUSG00000041570
rattus_norvegicus	Camsap2	ENSRNOG00000008741
drosophila_melanogaster	Patronin	FBGN0263197
caenorhabditis_elegans		WBGENE00004121

Paralogs (2): CAMSAP3 (ENSG00000076826), CAMSAP1 (ENSG00000130559)

Protein

Protein identifiers

Calmodulin-regulated spectrin-associated protein 2 — Q08AD1 (reviewed: Q08AD1)

Alternative names: Calmodulin-regulated spectrin-associated protein 1-like protein 1

All UniProt accessions (3): Q08AD1, H0Y4Z1, H0YE13

UniProt curated annotations — full annotation on UniProt →

Function. Key microtubule-organizing protein that specifically binds the minus-end of non-centrosomal microtubules and regulates their dynamics and organization. Specifically recognizes growing microtubule minus-ends and autonomously decorates and stabilizes microtubule lattice formed by microtubule minus-end polymerization. Acts on free microtubule minus-ends that are not capped by microtubule-nucleating proteins or other factors and protects microtubule minus-ends from depolymerization. In addition, it also reduces the velocity of microtubule polymerization. Through the microtubule cytoskeleton, also regulates the organization of cellular organelles including the Golgi and the early endosomes. Essential for the tethering, but not for nucleation of non-centrosomal microtubules at the Golgi: together with Golgi-associated proteins AKAP9 and PDE4DIP, required to tether non-centrosomal minus-end microtubules to the Golgi, an important step for polarized cell movement. Also acts as a regulator of neuronal polarity and development: localizes to non-centrosomal microtubule minus-ends in neurons and stabilizes non-centrosomal microtubules, which is required for neuronal polarity, axon specification and dendritic branch formation. Through the microtubule cytoskeleton, regulates the autophagosome transport.

Subunit / interactions. Interacts with CAMSAP3. Interacts with KATNA1 and KATNB1; leading to regulate the length of CAMSAP2-decorated microtubule stretches. Interacts with a complex formed by AKAP9 and PDE4DIP isoform 13/MMG8/SMYLE, which recruits CAMSAP2 to the Golgi. Interacts with MAPRE1/EB1.

Subcellular location. Cytoplasm. Cytoskeleton. Golgi apparatus. Cilium basal body.

Disease relevance. Defects in CAMSAP2 may be a cause of susceptibility to epilepsy in the Chinese population.

Domain organisation. The CKK domain binds microtubules and specifically recognizes the minus-end of microtubules. The MBD (microtubule-binding domain) region can recognize some features of the microtubule lattice, which might contribute to the specific decoration of growing microtubule minus-ends by CAMSAP2.

Similarity. Belongs to the CAMSAP1 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q08AD1-1	1	yes
Q08AD1-2	2
Q08AD1-3	3

RefSeq proteins (4): NP_001284636, NP_001284637, NP_001376567, NP_982284* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001715	CH_dom	Domain
IPR011033	PRC_barrel-like_sf	Homologous_superfamily
IPR014797	CKK_CAMSAP	Domain
IPR022613	CH_CAMSAP_2	Domain
IPR031372	CAMSAP_CC1	Conserved_site
IPR032940	CAMSAP	Family
IPR036872	CH_dom_sf	Homologous_superfamily
IPR038209	CKK_dom_sf	Homologous_superfamily
IPR058042	CAMSAP_N	Domain

Pfam: PF08683, PF11971, PF17095, PF25532

UniProt features (57 total): modified residue 22, compositionally biased region 11, region of interest 9, sequence variant 5, coiled-coil region 3, domain 2, splice variant 2, sequence conflict 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q08AD1-F1	57.60	0.19

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 (22): 416, 418, 426, 464, 598, 599, 611, 673, 678, 680, 862, 931, 936, 997, 1002, 1004, 1008, 1019, 1148, 1313 …

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 345 (showing top): WENDT_COHESIN_TARGETS_UP, GOBP_DENDRITE_DEVELOPMENT, GCACCTT_MIR18A_MIR18B, GOBP_REGULATION_OF_GOLGI_ORGANIZATION, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, GOBP_CYTOPLASMIC_MICROTUBULE_ORGANIZATION, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, TATTATA_MIR374, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, MISSIAGLIA_REGULATED_BY_METHYLATION_UP, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, ONKEN_UVEAL_MELANOMA_UP

GO Biological Process (9): microtubule cytoskeleton organization (GO:0000226), negative regulation of microtubule depolymerization (GO:0007026), regulation of microtubule polymerization (GO:0031113), cytoplasmic microtubule organization (GO:0031122), regulation of organelle organization (GO:0033043), regulation of dendrite development (GO:0050773), axon development (GO:0061564), regulation of Golgi organization (GO:1903358), neuron projection development (GO:0031175)

GO Molecular Function (5): calmodulin binding (GO:0005516), spectrin binding (GO:0030507), microtubule minus-end binding (GO:0051011), protein binding (GO:0005515), microtubule binding (GO:0008017)

GO Cellular Component (10): Golgi apparatus (GO:0005794), cytosol (GO:0005829), ciliary basal body (GO:0036064), microtubule end (GO:1990752), cytoplasm (GO:0005737), centrosome (GO:0005813), cytoskeleton (GO:0005856), microtubule (GO:0005874), microtubule minus-end (GO:0036449), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cytoplasm	2
microtubule organizing center	2
cytoskeleton organization	1
microtubule-based process	1
microtubule depolymerization	1
negative regulation of microtubule polymerization or depolymerization	1
regulation of microtubule depolymerization	1
negative regulation of protein depolymerization	1
negative regulation of supramolecular fiber organization	1
regulation of microtubule polymerization or depolymerization	1
regulation of protein polymerization	1
microtubule polymerization	1
regulation of supramolecular fiber organization	1
microtubule cytoskeleton organization	1
supramolecular fiber organization	1
organelle organization	1
regulation of cellular component organization	1
regulation of neuron projection development	1
dendrite development	1
regulation of developmental process	1
neuron projection development	1
Golgi organization	1
regulation of organelle organization	1
neuron development	1
plasma membrane bounded cell projection organization	1
protein binding	1
cytoskeletal protein binding	1
protein-containing complex binding	1
microtubule binding	1
binding	1
tubulin binding	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cilium	1
microtubule	1
intracellular anatomical structure	1
centriole	1
intracellular membraneless organelle	1
microtubule cytoskeleton	1

Protein interactions and networks

STRING

1052 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CAMSAP2	TRIM46	Q7Z4K8	616
CAMSAP2	ACE2	Q9BYF1	560
CAMSAP2	MAPRE3	Q9UPY8	537
CAMSAP2	GCC2	Q8IWJ2	520
CAMSAP2	MEMO1	Q9Y316	520
CAMSAP2	PDE4DIP	Q5VU43	494
CAMSAP2	NIN	Q8N4C6	478
CAMSAP2	MED14	O60244	460
CAMSAP2	DDX59	Q5T1V6	460
CAMSAP2	SPINK8	P0C7L1	456
CAMSAP2	AKAP9	Q99996	446
CAMSAP2	TIMELESS	Q9UNS1	443
CAMSAP2	SMG1	Q96Q15	441
CAMSAP2	MAPRE1	Q15691	440
CAMSAP2	MAP7	Q14244	439

IntAct

116 interactions, top by confidence:

A	B	Type	Score
YWHAQ	WDR62	psi-mi:“MI:0914”(association)	0.830
CCDC22	VPS26C	psi-mi:“MI:0914”(association)	0.790
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
YWHAB	BLTP3B	psi-mi:“MI:2364”(proximity)	0.610
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
CEP104	CCDC66	psi-mi:“MI:2364”(proximity)	0.540
YWHAQ	IGLC7	psi-mi:“MI:0914”(association)	0.530
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
SYCE3	RER1	psi-mi:“MI:0914”(association)	0.530
PNMA2	CCDC85C	psi-mi:“MI:0914”(association)	0.530
EEF1D	CAMSAP2	psi-mi:“MI:0915”(physical association)	0.520
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
ORF6	CAMSAP2	psi-mi:“MI:0915”(physical association)	0.400
CAMSAP2	HNRNPC	psi-mi:“MI:0915”(physical association)	0.400
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
EGLN3	FAM168B	psi-mi:“MI:0914”(association)	0.350
APP	ESYT2	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
YWHAG	C1orf226	psi-mi:“MI:0914”(association)	0.350
P		psi-mi:“MI:0914”(association)	0.350
CEP192	WASL	psi-mi:“MI:0914”(association)	0.350
ARID1B	RTCA	psi-mi:“MI:0914”(association)	0.350
CACNA1C	SNRPGP15	psi-mi:“MI:0914”(association)	0.350
TUBB4B	TUBA1B	psi-mi:“MI:0914”(association)	0.350
YWHAB	BRAF	psi-mi:“MI:0914”(association)	0.350

BioGRID (200): CAMSAP2 (Biochemical Activity), CAMSAP2 (Affinity Capture-MS), CAMSAP2 (Proximity Label-MS), CAMSAP2 (Proximity Label-MS), CAMSAP2 (Proximity Label-MS), CAMSAP2 (Proximity Label-MS), CAMSAP2 (Proximity Label-MS), CAMSAP2 (Proximity Label-MS), CAMSAP2 (Proximity Label-MS), CAMSAP2 (Proximity Label-MS), CAMSAP2 (Affinity Capture-MS), CAMSAP2 (Affinity Capture-MS), CAMSAP2 (Affinity Capture-MS), CAMSAP2 (Affinity Capture-MS), CAMSAP2 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GVH7, A6PVS8, A8DZJ1, A9Q751, D3ZSP7, D4AEC2, Q08AD1, Q08CX2, Q14DL3, Q2T9P0, Q2TA00, Q32KQ1, Q3UZ57, Q3V0J4, Q4G0U5, Q4R7B1, Q4R7Z7, Q5S003, Q5SUV2, Q5T1B0, Q5ZLS8, Q63164, Q66HC0, Q69CM7, Q6AXP3, Q6AYL8, Q6IRN6, Q6NXP0, Q6Q759, Q80X60, Q86WZ0, Q8C1B1, Q8C4J0, Q8C636, Q8CDN1, Q8CDU5, Q8IWF9, Q8N7B9, Q8N7U6, Q8ND61

Diamond homologs: A1ZAU8, A2AHC3, A5WUN7, D3Z8E6, D4AEC2, Q08AD1, Q5T5Y3, Q6IRN6, Q80VC9, Q8C1B1, Q9P1Y5, U4PAZ9

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 116 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
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	8	69.8×	3e-11
Activation of BAD and translocation to mitochondria	7	69.2×	2e-10
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	61.1×	5e-10
Activation of BH3-only proteins	7	45.1×	4e-09
RHO GTPases activate PKNs	8	33.0×	3e-09
Intrinsic Pathway for Apoptosis	7	26.6×	1e-07
Translocation of SLC2A4 (GLUT4) to the plasma membrane	11	22.1×	2e-10
FOXO-mediated transcription	5	21.8×	4e-05

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	6	20.9×	2e-04
cerebral cortex development	6	11.7×	3e-03
intracellular protein localization	10	10.0×	5e-05
cell division	11	4.8×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	149
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

3359 predictions. Top by Δscore:

Variant	Effect	Δscore
1:200760836:TAGA:T	acceptor_loss	1.0000
1:200760837:A:AC	acceptor_loss	1.0000
1:200760837:A:AG	acceptor_gain	1.0000
1:200760838:G:GG	acceptor_gain	1.0000
1:200760838:GA:G	acceptor_gain	1.0000
1:200760838:GAA:G	acceptor_gain	1.0000
1:200760838:GAAA:G	acceptor_gain	1.0000
1:200760838:GAAAA:G	acceptor_gain	1.0000
1:200761095:GATG:G	donor_gain	1.0000
1:200761096:ATG:A	donor_gain	1.0000
1:200761099:G:A	donor_loss	1.0000
1:200761099:G:GG	donor_gain	1.0000
1:200761100:TGA:T	donor_loss	1.0000
1:200807370:TTTCA:T	acceptor_loss	1.0000
1:200807371:TTCA:T	acceptor_loss	1.0000
1:200807372:TCAGA:T	acceptor_loss	1.0000
1:200807373:CA:C	acceptor_loss	1.0000
1:200807375:GA:G	acceptor_gain	1.0000
1:200807375:GAGT:G	acceptor_gain	1.0000
1:200807533:ATAAG:A	donor_loss	1.0000
1:200807534:TAAGG:T	donor_loss	1.0000
1:200807535:AAG:A	donor_loss	1.0000
1:200807536:AGGT:A	donor_loss	1.0000
1:200807537:GGTA:G	donor_loss	1.0000
1:200807538:G:GA	donor_loss	1.0000
1:200807539:T:A	donor_loss	1.0000
1:200815558:AAG:A	acceptor_gain	1.0000
1:200815559:A:G	acceptor_gain	1.0000
1:200815634:G:GT	donor_gain	1.0000
1:200815638:TCAAA:T	donor_gain	1.0000

AlphaMissense

9800 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:200857354:T:A	I1365K	1.000
1:200857363:C:A	A1368D	1.000
1:200857376:C:G	C1372W	1.000
1:200857387:G:A	G1376E	1.000
1:200857791:T:G	L1401W	1.000
1:200857794:T:C	F1402S	1.000
1:200857797:G:C	R1403P	1.000
1:200857815:T:C	F1409S	1.000
1:200857818:G:C	R1410T	1.000
1:200857826:T:G	Y1413D	1.000
1:200857869:G:A	G1427E	1.000
1:200857874:G:C	G1429R	1.000
1:200857875:G:A	G1429D	1.000
1:200857916:A:G	K1443E	1.000
1:200857919:T:C	Y1444H	1.000
1:200857919:T:G	Y1444D	1.000
1:200857920:A:C	Y1444S	1.000
1:200857940:T:C	F1451L	1.000
1:200857941:T:C	F1451S	1.000
1:200857942:T:A	F1451L	1.000
1:200857942:T:G	F1451L	1.000
1:200857977:T:A	V1463D	1.000
1:200857979:G:C	D1464H	1.000
1:200857982:G:C	A1465P	1.000
1:200857983:C:A	A1465E	1.000
1:200858006:T:A	W1473R	1.000
1:200858006:T:C	W1473R	1.000
1:200761076:T:C	L126P	0.999
1:200848834:T:C	F700L	0.999
1:200848835:T:C	F700S	0.999

dbSNP variants (sampled 300 via entrez): RS1000058825 (1:200749157 G>C), RS1000058907 (1:200761925 A>G), RS1000081365 (1:200792848 C>T), RS1000100203 (1:200802992 T>C), RS1000187382 (1:200823341 A>G), RS1000189023 (1:200774834 G>A), RS1000234573 (1:200804463 A>C,T), RS1000249313 (1:200804661 C>T), RS1000249833 (1:200825213 GT>G), RS1000274745 (1:200810014 A>G), RS1000281033 (1:200755361 A>G), RS1000294658 (1:200830362 A>G), RS1000295357 (1:200853133 C>T), RS1000317335 (1:200751754 G>A), RS1000319349 (1:200816162 C>T)

Disease associations

OMIM: gene MIM:613775 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): premature menopause (MONDO:0001119)

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST001329_1	Epilepsy	1.000000e-08
GCST006979_966	Heel bone mineral density	1.000000e-18
GCST007932_73	Medication use (thyroid preparations)	4.000000e-10
GCST009391_1702	Metabolite levels	1.000000e-06
GCST010002_373	Refractive error	1.000000e-52

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0009270	heel bone mineral density
EFO:0009933	Thyroid preparation use measurement
EFO:0010340	cholesteryl ester 14:0 measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008594	Menopause, Premature	C12.050.351.500.056.630.250; C12.100.250.056.630.250; G08.686.157.500.500; G08.686.841.249.500.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects binding, increases reaction, increases expression	2
Cyclosporine	increases expression	2
FR900359	increases phosphorylation	1
bisphenol F	increases expression, affects cotreatment	1
testosterone enanthate	affects expression	1
bisphenol A	decreases expression	1
arsenite	affects binding, decreases reaction	1
perfluorooctanoic acid	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
chloropicrin	increases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
perfluorohexanesulfonic acid	decreases expression	1
abrine	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
PCI 5002	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Vorinostat	decreases expression	1
Arsenic	affects methylation	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases expression	1
Caffeine	affects phosphorylation	1
Cisplatin	affects cotreatment, decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Diethylstilbestrol	decreases expression	1
Gallic Acid	increases expression	1
Hydrogen Peroxide	affects expression	1
Indomethacin	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Thiram	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
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
NCT00140998	PHASE3	COMPLETED	Estrogen Treatment (Oral vs. Patches) in Turner Syndrome
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
NCT02912104	PHASE1	COMPLETED	A Therapeutic Trial of Human Amniotic Epithelial Cells Transplantation for Primary Ovarian Failure
NCT03178695	PHASE1	COMPLETED	Inovium Ovarian Rejuvenation Trials
NCT04815213	PHASE1	ACTIVE_NOT_RECRUITING	The Use of Expandeded Mesenchymal Stromal Cells (MSC) in Premature Ovarian Failure (POF) in Adult Humans
NCT05138367	PHASE1	COMPLETED	Effects of UCA-PSCs in Women With POF
NCT06132542	PHASE1	UNKNOWN	Autologous ADMSC Transplantation in Patients With POI
NCT00948857	PHASE2/PHASE3	TERMINATED	Dehydroepiandrosterone (DHEA) Treatment and Premature Ovarian Failure (POF)
NCT04031456	PHASE2/PHASE3	RECRUITING	Autologous PRP Infusion May Restore Ovarian Function and May Promote Folliculogenesis in POI Patients
NCT02043743	PHASE1/PHASE2	UNKNOWN	Autologous Stem Cells Transplantation in Patients With Idiopathic and Drug Induced Premature Ovarian Failure
NCT02062931	PHASE1/PHASE2	UNKNOWN	Autologous Mesenchymal Stem Cells Transplantation In Women With Premature Ovarian Failure
NCT02151890	PHASE1/PHASE2	COMPLETED	Pregnancy After Stem Cell Transplantation in Premature Ovarian Failure
NCT02372474	PHASE1/PHASE2	COMPLETED	It is a Real The First Baby Of Autologous Stem Cell Therapy in Premature Ovarian Failure
NCT02603744	PHASE1/PHASE2	UNKNOWN	Autologous Adipose Derived Mesenchymal Stromal Cells Transplantation in Women With Premature Ovarian Failure (POF)
NCT02644447	PHASE1/PHASE2	COMPLETED	Transplantation of HUC-MSCs With Injectable Collagen Scaffold for POF
NCT03069209	PHASE1/PHASE2	UNKNOWN	Autologous Bone Marrow-Derived Stem Cell Transplantation in Patients With Premature Ovarian Failure (POF)
NCT03985462	PHASE1/PHASE2	WITHDRAWN	Very Small Embryonic-like Stem Cells for Ovary
NCT04009473	PHASE1/PHASE2	UNKNOWN	Stem Cell Therapy and Growth Factor Ovarian in Vitro Activation
NCT04071574	PHASE1/PHASE2	COMPLETED	Comparative Study on the Efficacy of Ovarian Stimulation Protocols on the Success Rate of ICSI in Female Infertility
NCT04922398	PHASE1/PHASE2	UNKNOWN	Ovarian Injection of PRP (Platelet -Rich Plasma) Vs Normal Saline in Premature Ovarian Insufficiency
NCT05462379	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Autologous Heterotopic Fresh Ovarian Graft in Woman With LACC Eligible for Pelvic Radiotherapy Treatment.
NCT06202547	PHASE1/PHASE2	UNKNOWN	Intra-ovarian Injection of MSC-EVs in Idiopathic Premature Ovarian Failure
NCT01129947	EARLY_PHASE1	WITHDRAWN	The Use of DHEA in Women With Premature Ovarian Failure
NCT05522634	EARLY_PHASE1	UNKNOWN	A Clinical Study of Chinese Herbal Compound TJAOA101 in the Treatment of Premature Ovarian Insufficiency
NCT07308327	EARLY_PHASE1	ACTIVE_NOT_RECRUITING	The Influence of Gut Microbiota on Ovarian Function: A Single-center, Randomized,Double Blind, Parallel-controlled, Exploratory Clinical Trial
NCT00001275	Not specified	COMPLETED	Ovarian Follicle Function in Patients With Primary Ovarian Failure
NCT00001306	Not specified	COMPLETED	Steroid Therapy in Autoimmune Premature Ovarian Failure
NCT00006156	Not specified	COMPLETED	Feasibility Study for Development of an Early Test for Ovarian Failure
NCT00119925	Not specified	UNKNOWN	‘SPRING’-Study: Subfertility Guidelines: Patient Related Implementation in the Netherlands Among Gynaecologists