SERPINA12

Summary

SERPINA12 (serpin family A member 12, HGNC:18359) is a protein-coding gene on chromosome 14q32.13, encoding Serpin A12 (Q8IW75). Adipokine that modulates insulin action by specifically inhibiting its target protease KLK7 in white adipose tissues.

Enables molecular function inhibitor activity. Predicted to act upstream of or within negative regulation of gluconeogenesis; positive regulation of signal transduction; and regulation of lipid metabolic process. Predicted to be located in extracellular region and plasma membrane. Predicted to be active in extracellular space.

Source: NCBI Gene 145264 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hereditary palmoplantar keratoderma, Gamborg-Nielsen type (Supportive, GenCC)
• GWAS associations: 5
• Clinical variants (ClinVar): 82 total — 1 pathogenic
• MANE Select transcript: NM_001382267

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18359
Approved symbol	SERPINA12
Name	serpin family A member 12
Location	14q32.13
Locus type	gene with protein product
Status	Approved
Aliases	OL-64, Vaspin
Ensembl gene	ENSG00000165953
Ensembl biotype	protein_coding
OMIM	617471
Entrez	145264

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000341228, ENST00000556881, ENST00000677451, ENST00000861504, ENST00000861505

RefSeq mRNA: 3 — MANE Select: NM_001382267 NM_001304461, NM_001382267, NM_173850

CCDS: CCDS9926

Canonical transcript exons

ENST00000677451 — 5 exons

Exon	Start	End
ENSE00001098394	94496373	94496643
ENSE00001098404	94489620	94489767
ENSE00002468086	94497764	94498430
ENSE00003904296	94509342	94509469
ENSE00003906835	94487279	94487494

Expression profiles

Bgee: expression breadth ubiquitous, 120 present calls, max score 97.90.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skin of leg	UBERON:0001511	97.90	gold quality
upper leg skin	UBERON:0004262	97.59	gold quality
zone of skin	UBERON:0000014	97.49	gold quality
skin of hip	UBERON:0001554	97.43	gold quality
skin of abdomen	UBERON:0001416	97.37	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.83	gold quality
nipple	UBERON:0002030	79.63	gold quality
penis	UBERON:0000989	74.17	gold quality
mammalian vulva	UBERON:0000997	73.95	silver quality
right lobe of liver	UBERON:0001114	63.50	gold quality
right uterine tube	UBERON:0001302	55.62	gold quality
liver	UBERON:0002107	53.21	gold quality
vagina	UBERON:0000996	52.92	gold quality
gastrocnemius	UBERON:0001388	51.84	gold quality
epithelium of nasopharynx	UBERON:0001951	51.65	gold quality
lower esophagus mucosa	UBERON:0035834	49.68	gold quality
muscle of leg	UBERON:0001383	48.39	gold quality
vastus lateralis	UBERON:0001379	48.35	gold quality
quadriceps femoris	UBERON:0001377	48.17	gold quality
heart left ventricle	UBERON:0002084	47.93	gold quality
adrenal tissue	UBERON:0018303	47.87	gold quality
cardiac ventricle	UBERON:0002082	47.66	gold quality
left ovary	UBERON:0002119	46.62	gold quality
subthalamic nucleus	UBERON:0001906	46.43	gold quality
apex of heart	UBERON:0002098	46.31	gold quality
popliteal artery	UBERON:0002250	46.04	gold quality
tibial artery	UBERON:0007610	45.93	gold quality
cardia of stomach	UBERON:0001162	45.81	gold quality
right adrenal gland cortex	UBERON:0035827	45.43	gold quality
right atrium auricular region	UBERON:0006631	44.46	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.79

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 40)

• Induction of human vaspin mRNA expression in adipose tissue is regulated in a fat depot-specific manner and could be associated with parameters of obesity, insulin resistance, and glucose metabolism. (PMID:16298335)
• Low circulating vaspin correlates with a high fitness level, whereas physical training in untrained individuals causes increased vaspin serum concentrations. (PMID:17991760)
• Elevated serum and omental adipose tissue levels of vaspin in overweight polycystic ovary syndrome women and ex vivo regulation of vaspin expression. (PMID:18375437)
• results demonstrate a significant association of vaspin SNP rs2236242 with T2DM in the KORA F3 study with the AA genotype bearing an increased risk (adjusted OR 2.35 [1.59; 3.46] versus AT/TT). (PMID:18726871)
• may be the compensatory molecule in the pathogenesis of metabolic syndrome. (review) (PMID:18800627)
• Low vaspin serum concentrations correlate with recently experienced ischemic events in patients with carotid stenosis despite the lack of an association between circulating vaspin and parameters of atherosclerosis severity. (PMID:18848328)
• Serum vaspin concentrations in premenopausal women are not affected by polycystic ovary syndrome, obesity, or glucose tolerance disorders. (PMID:19114623)
• Higher vaspin(SERPINA12) and lower adiponectin levels in obese children: these adipokines are significantly correlated with insulin sensitivity indices in this age. (PMID:19356820)
• Vaspin is expressed in the human placenta and is regulated by nutrtional status. (PMID:19554505)
• the first study to show that high body fatness along with low CRF might contribute to increased vaspin concentrations in Korean young men. (PMID:19816707)
• Serum vaspin level is higher in diabetic patients than that in NGT subjects in women. Age predicts serum vaspin level in NGT subjects, while PG2h is independently associated with vaspin in diabetic patients. (PMID:19951565)
• Our results support the existence of a sexual dimorphism regarding circulating vaspin but find no major role for vaspin concerning insulin sensitivity in nondiabetic humans. (PMID:19952124)
• Serum vaspin level is one of the predictors for insulin resistance (PMID:20018186)
• Circulating vaspin levels are not significantly different between gestational diabetes mellitus, preeclampsia, and control subjects and do not correlate with insulin sensitivity in pregnant subjects (PMID:20045145)
• visceral adipose tissue area was independently correlated with serum vaspin concentrations in the higher insulin resistance group (PMID:20060144)
• Vaspin serum concentrations are altered in patients with non-alcoholic fatty liver disease. (PMID:20095887)
• Serum vaspin levels have a meal-related diurnal variation, suggesting a role for vaspin in metabolic regulation (PMID:20156923)
• lower maternal vaspin concentrations in cases of vaginal delivery may be attributed to spontaneous term delivery inflammation (PMID:20488498)
• Serum vaspin levels are raised in patients with nonalcoholic fatty liver disease regardless of potential confounders and represent an independent predictor of liver fibrosis scores (PMID:20580037)
• both vaspin and visfatin/Nampt might play an important role in the pathogenesis of T2DM. (PMID:20605615)
• Presence of increased vaspin and higher insulin resistance values in women with polycystic ovary syndrome could contribute to increased diabetogenic and atherogenic risk in these patients. (PMID:20626239)
• Decreased vaspin and increased visfatin serum levels were observed in asymptomatic patients with coronary artery disease. (PMID:20850423)
• Vaspin serum concentrations are decreased by exercise-induced oxidative stress, but not by exercise-associated improvement in insulin sensitivity. (PMID:20975299)
• Letter: serum vaspin levels were not significantly different in patients with Kawasaki disease compared to controls. (PMID:21442174)
• there is a complex interplay between epicardial fat thickness, serum vaspin, and liver histology in promoting an impaired hyperemic stimulation of coronary blood flow in patients with NAFLD (PMID:21513939)
• Higher plasma vaspin concentrations are significantly associated with metabolic syndrome in men. In women, vaspin concentrations are associated with coronary atherosclerosis. (PMID:21545478)
• Vaspin expression in abdominal adipose tissue was adipocyte-specific and vaspin expression in subcutaneous adipose tissue decreased as visceral adipose tissue area increased. (PMID:21646731)
• Data indicating a possible role of leptin, adiponectin, visfatin, chemerin and vaspin in the pathogenesis of chronic hepatitis are summarized. (PMID:21738955)
• We herein present novel data indicating SERPINA12 levels are neither altered in overt and subclinical hypothyroidism (PMID:21798959)
• The present study indicates that vaspin protects vascular endothelial cells from FFA-induced apoptosis through upregulation of the PI3-kinase/Akt signaling pathway. (PMID:21893030)
• Our study is the first report on the new adipokines vaspin and omentin in patients with JIA, and it shows that omentin is significantly higher in juvenile idiopathic arthritis patients in comparison with healthy controls. (PMID:22032341)
• circulating vaspin levels have an effect on metabolic variables in elderly twins (PMID:22116078)
• Serum vaspin concentration seems to reflect intensity of liver angiogenesis in chronic hepatitis C patients. (PMID:22246907)
• The anti-inflammatory adipokine vaspin is discussed as a new link between inflammation and obesity. We demonstrate that - different from healthy controls - vaspin serum levels in patients with psoriasis were body mass index independent. (PMID:22417310)
• Serum vaspin levels were related to insulin resistance, and higher levels of serum vaspin in 7% of the Japanese population are closely linked to minor allele sequence (A) of rs77060950. (PMID:22539588)
• Variability in serum vaspin concentrations might be explained by its genetic variants. (PMID:22907691)
• Finding showed that there are significant differences in genotype frequencies between the groups regarding vaspin rs2236242 polymorphism (chi(2)=18.74, p<0.0001). A significant protection against Metabolic syndrome was found for vaspin rs2236242 in allele and genotypes (PMID:22982016)
• Serum vaspin cannot independently predict gestational diabetes mellitus and it is not affected by the degree of glucose metabolism deregulation or the exogenous administration of insulin. (PMID:23041430)
• Variants of the vaspin gene are associated with serum vaspin levels and with the risk for coronary artery disease in the Chinese population. (PMID:23123830)
• Vaspin inhibited the apoptosis of human osteoblasts through ERK signaling pathway. (PMID:23135225)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Serpina12	ENSMUSG00000041567
rattus_norvegicus	Serpina12	ENSRNOG00000042634

Paralogs (36): SERPINB1 (ENSG00000021355), SERPINB3 (ENSG00000057149), SERPIND1 (ENSG00000099937), SERPINA4 (ENSG00000100665), SERPINE1 (ENSG00000106366), SERPINI2 (ENSG00000114204), SERPINC1 (ENSG00000117601), SERPINA7 (ENSG00000123561), SERPINB6 (ENSG00000124570), SERPINF1 (ENSG00000132386), AGT (ENSG00000135744), SERPINE2 (ENSG00000135919), SERPINA10 (ENSG00000140093), SERPING1 (ENSG00000149131), SERPINH1 (ENSG00000149257), SERPINI1 (ENSG00000163536), SERPINB7 (ENSG00000166396), SERPINB8 (ENSG00000166401), SERPINB12 (ENSG00000166634), SERPINF2 (ENSG00000167711), SERPINA9 (ENSG00000170054), SERPINA6 (ENSG00000170099), SERPINB9 (ENSG00000170542), SERPINA11 (ENSG00000186910), SERPINA5 (ENSG00000188488), SERPINA3 (ENSG00000196136), SERPINA1 (ENSG00000197249), SERPINB2 (ENSG00000197632), SERPINB13 (ENSG00000197641), SERPINB11 (ENSG00000206072), SERPINB4 (ENSG00000206073), SERPINB5 (ENSG00000206075), HMSD (ENSG00000221887), SERPINB10 (ENSG00000242550), SERPINE3 (ENSG00000253309), SERPINA2 (ENSG00000258597)

Protein

Protein identifiers

Serpin A12 — Q8IW75 (reviewed: Q8IW75)

Alternative names: OL-64, Visceral adipose tissue-derived serine protease inhibitor, Visceral adipose-specific serpin

All UniProt accessions (1): Q8IW75

UniProt curated annotations — full annotation on UniProt →

Function. Adipokine that modulates insulin action by specifically inhibiting its target protease KLK7 in white adipose tissues.

Subunit / interactions. Forms a stable complex with KLK7.

Subcellular location. Secreted.

Tissue specificity. Expressed in visceral adipose tissues.

Post-translational modifications. Glycosylation slightly decreases affinity for heparin, but otherwise has no significant effect on KLK7 inhibitory activity or thermal stability of the protein.

Activity regulation. Inhibition of KLK7 is enhanced by heparin.

Domain organisation. The reactive center loop (RCL) extends out from the body of the protein and directs binding to the target protease. The protease cleaves the serpin at the reactive site within the RCL, establishing a covalent linkage between the carboxyl group of the serpin reactive site and the serine hydroxyl of the protease. The resulting inactive serpin-protease complex is highly stable.

Similarity. Belongs to the serpin family.

RefSeq proteins (3): NP_001291390, NP_001369196, NP_776249 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000215	Serpin_fam	Family
IPR023796	Serpin_dom	Domain
IPR036186	Serpin_sf	Homologous_superfamily
IPR042178	Serpin_sf_1	Homologous_superfamily
IPR042185	Serpin_sf_2	Homologous_superfamily

Pfam: PF00079

UniProt features (52 total): strand 16, helix 12, mutagenesis site 9, turn 5, glycosylation site 3, sequence variant 3, signal peptide 1, chain 1, region of interest 1, site 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
4IF8	X-RAY DIFFRACTION	2.08
4Y3K	X-RAY DIFFRACTION	2.2
4Y40	X-RAY DIFFRACTION	2.2
9IH0	X-RAY DIFFRACTION	2.26
5EI0	X-RAY DIFFRACTION	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IW75-F1	88.98	0.77

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 378–379 (cleavage)

Glycosylation sites (3): 221, 233, 267

Mutagenesis-validated functional residues (9):

Position	Phenotype
221	reduced n-glycosylation. loss of n-glycosylation; when associated with a-233 and a-267.
233	reduced n-glycosylation. loss of n-glycosylation; when associated with a-221 and a-267.
267	reduced n-glycosylation. loss of n-glycosylation; when associated with a-221 and a-233.
302	significantly impairs klk7 inhibition activity. slightly enhances klk7 inhibition activity; when associated with s-379.
305	results in formation of an artificial disulfide bond which stabilizes the reactive center loop and enhances klk7 inhibit
365	fails to inhibit klk7 activity. increased protein stability in cleaved form and conformational changes which may allow e
369	fails to inhibit klk7 activity. increased protein stability in cleaved form and conformational changes which may allow e
379	significantly enhances klk7 inhibition activity. slightly enhances klk7 inhibition activity; when associated with e-302.
383	results in formation of an artificial disulfide bond which stabilizes the reactive center loop and enhances klk7 inhibit

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 103 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_TRIGLYCERIDE_METABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_LIPID_METABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_LIPID_BIOSYNTHETIC_PROCESS, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_CELLULAR_RESPONSE_TO_INSULIN_STIMULUS, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, GOBP_REGULATION_OF_LIPID_BIOSYNTHETIC_PROCESS, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, MARTINEZ_RB1_TARGETS_UP, GOBP_REGULATION_OF_LIPID_METABOLIC_PROCESS, GOBP_CELLULAR_RESPONSE_TO_HORMONE_STIMULUS, GOBP_RESPONSE_TO_INSULIN, GOBP_REGULATION_OF_CARBOHYDRATE_METABOLIC_PROCESS, GOBP_MONOSACCHARIDE_BIOSYNTHETIC_PROCESS

GO Biological Process (9): gluconeogenesis (GO:0006094), lipid biosynthetic process (GO:0008610), phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0043491), negative regulation of gluconeogenesis (GO:0045721), positive regulation of insulin receptor signaling pathway (GO:0046628), negative regulation of lipid biosynthetic process (GO:0051055), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), regulation of cholesterol metabolic process (GO:0090181), regulation of triglyceride metabolic process (GO:0090207)

GO Molecular Function (4): serine-type endopeptidase inhibitor activity (GO:0004867), molecular function inhibitor activity (GO:0140678), protein binding (GO:0005515), peptidase inhibitor activity (GO:0030414)

GO Cellular Component (3): obsolete extracellular space (GO:0005615), plasma membrane (GO:0005886), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
negative regulation of biosynthetic process	2
glucose metabolic process	1
hexose biosynthetic process	1
lipid metabolic process	1
biosynthetic process	1
intracellular signaling cassette	1
gluconeogenesis	1
regulation of gluconeogenesis	1
negative regulation of carbohydrate metabolic process	1
negative regulation of small molecule metabolic process	1
insulin receptor signaling pathway	1
positive regulation of signal transduction	1
regulation of insulin receptor signaling pathway	1
positive regulation of cellular response to insulin stimulus	1
lipid biosynthetic process	1
negative regulation of lipid metabolic process	1
regulation of lipid biosynthetic process	1
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
positive regulation of intracellular signal transduction	1
cholesterol metabolic process	1
regulation of steroid metabolic process	1
regulation of small molecule metabolic process	1
triglyceride metabolic process	1
regulation of lipid metabolic process	1
serine-type endopeptidase activity	1
endopeptidase inhibitor activity	1
molecular function regulator activity	1
binding	1
enzyme inhibitor activity	1
peptidase activity	1
peptidase regulator activity	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

846 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SERPINA12	ITLN1	Q8WWA0	840
SERPINA12	RARRES2	Q99969	790
SERPINA12	NAMPT	P43490	769
SERPINA12	HSPA5	P11021	768
SERPINA12	RETN	Q9HD89	720
SERPINA12	RETNLB	Q9BQ08	720
SERPINA12	ADIPOQ	Q15848	720
SERPINA12	APLN	Q9ULZ1	712
SERPINA12	LEP	P41159	702
SERPINA12	RBP4	P02753	666
SERPINA12	INS	P01308	604
SERPINA12	KLK7	P49862	586
SERPINA12	FGF21	Q9NSA1	537
SERPINA12	GRN	P23781	528
SERPINA12	CFD	P00746	479

IntAct

110 interactions, top by confidence:

A	B	Type	Score
FANCG	FANCA	psi-mi:“MI:0914”(association)	0.960
ASH2L	KMT2D	psi-mi:“MI:0914”(association)	0.890
AMPH	BIN1	psi-mi:“MI:0914”(association)	0.740
SERPINA12	LAMB1	psi-mi:“MI:0915”(physical association)	0.710
POLR2L	RCCD1	psi-mi:“MI:0914”(association)	0.640
CCNC	MED19	psi-mi:“MI:0914”(association)	0.640
ALDH3A1	RCCD1	psi-mi:“MI:0914”(association)	0.640
CD68	LGALS1	psi-mi:“MI:0914”(association)	0.640
STK11	KDM4A	psi-mi:“MI:0914”(association)	0.640
CFAP298	PEX7	psi-mi:“MI:0914”(association)	0.620
ZSCAN12	A2ML1	psi-mi:“MI:0914”(association)	0.530
FTH1	A2ML1	psi-mi:“MI:0914”(association)	0.530
GMCL1	A2ML1	psi-mi:“MI:0914”(association)	0.530
SERPINA12	TSPAN6	psi-mi:“MI:0914”(association)	0.530
KIR3DS1	PPL	psi-mi:“MI:0914”(association)	0.530
NDUFS5	NDUFS4	psi-mi:“MI:0914”(association)	0.530
DTL	DNAJA2	psi-mi:“MI:0914”(association)	0.530
TOX4	ALOX12B	psi-mi:“MI:0914”(association)	0.530
CUL1	HAL	psi-mi:“MI:0914”(association)	0.530
EVA1C	STK25	psi-mi:“MI:0914”(association)	0.530
MRPS18C	MRPS14	psi-mi:“MI:0914”(association)	0.530
DENND1B	SERPINA12	psi-mi:“MI:0915”(physical association)	0.400
CEP15	SERPINA12	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (142): SERPINA12 (Affinity Capture-MS), SERPINA12 (Affinity Capture-MS), SERPINA12 (Affinity Capture-MS), SERPINA12 (Affinity Capture-MS), SERPINA12 (Affinity Capture-MS), SERPINA12 (Affinity Capture-MS), SERPINA12 (Affinity Capture-MS), SERPINA12 (Affinity Capture-MS), SERPINA12 (Affinity Capture-MS), SERPINA12 (Affinity Capture-MS), SERPINA12 (Affinity Capture-MS), SUSD5 (Affinity Capture-MS), KIAA1549 (Affinity Capture-MS), LAMB1 (Affinity Capture-MS), CTAGE5 (Affinity Capture-MS)

ESM2 similar proteins: A2I7M9, A2I7N0, A2I7N1, A2I7N2, A2I7N3, A6QPQ2, B2D1U1, E1BF81, O54762, P01011, P05154, P05544, P05545, P07759, P08185, P09006, P22323, P22324, P22325, P22599, P26595, P29621, P29622, P31211, P50451, P70458, Q00896, Q00897, Q00898, Q03044, Q03734, Q3ZEJ6, Q5I2A0, Q5R536, Q5R9E3, Q5RCR2, Q60396, Q63556, Q63969, Q64118

Diamond homologs: A2I7M9, A2I7N0, A2I7N1, A2I7N2, A2I7N3, A6QPQ2, B2D1U1, E1BF81, O00394, O54757, O54758, O54759, O54760, O54761, O54762, O54763, O75830, P01009, P01010, P01011, P05154, P05543, P05544, P05545, P05619, P07758, P07759, P08185, P09005, P09006, P12725, P17475, P20848, P22323, P22324, P22325, P22599, P23035, P23775, P26595

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	65
Likely benign	6
Benign	4

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2574604	NM_001382267.1(SERPINA12):c.1051G>T (p.Glu351Ter)	Pathogenic

SpliceAI

910 predictions. Top by Δscore:

Variant	Effect	Δscore
14:94489616:TTA:T	donor_loss	1.0000
14:94489617:TACCT:T	donor_loss	1.0000
14:94489619:CCTCG:C	donor_gain	1.0000
14:94489763:CGACC:C	acceptor_gain	1.0000
14:94489766:CC:C	acceptor_gain	1.0000
14:94489767:CC:C	acceptor_gain	1.0000
14:94496650:T:TC	acceptor_gain	1.0000
14:94487491:CAGC:C	acceptor_gain	0.9900
14:94489618:A:AC	donor_gain	0.9900
14:94489619:C:CC	donor_gain	0.9900
14:94489619:CCT:C	donor_gain	0.9900
14:94489764:GACCC:G	acceptor_gain	0.9900
14:94489765:ACCCT:A	acceptor_gain	0.9900
14:94489768:C:A	acceptor_loss	0.9900
14:94489768:C:CC	acceptor_gain	0.9900
14:94489768:C:T	acceptor_gain	0.9900
14:94489769:T:C	acceptor_loss	0.9900
14:94489776:T:TC	acceptor_gain	0.9900
14:94496368:TTTA:T	donor_loss	0.9900
14:94496370:TA:T	donor_loss	0.9900
14:94496371:ACCT:A	donor_loss	0.9900
14:94496372:CCT:C	donor_loss	0.9900
14:94496372:CCTG:C	donor_gain	0.9900
14:94496411:C:CT	donor_gain	0.9900
14:94496645:T:C	acceptor_gain	0.9900
14:94496645:T:TC	acceptor_gain	0.9900
14:94496650:T:C	acceptor_gain	0.9900
14:94504129:A:AC	donor_gain	0.9900
14:94504130:C:CC	donor_gain	0.9900
14:94504130:CAGTA:C	donor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000006577 (14:94488834 C>A), RS1000098962 (14:94516847 G>A), RS1000106741 (14:94493785 T>C), RS1000138140 (14:94493589 C>T), RS1000174173 (14:94519090 GTGT>G), RS1000566073 (14:94508452 G>A), RS1000814502 (14:94495856 G>A), RS1000936900 (14:94508725 C>G), RS1001102922 (14:94495580 A>T), RS1001146443 (14:94492508 C>G,T), RS1001235756 (14:94510660 A>C,G), RS1001287513 (14:94517089 G>A), RS1001290669 (14:94503962 T>C), RS1001404256 (14:94487498 CG>C), RS1001454660 (14:94491411 C>T)

Disease associations

OMIM: gene MIM:617471 | disease phenotypes: MIM:244850

GenCC curated gene-disease

Disease	Classification	Inheritance
hereditary palmoplantar keratoderma, Gamborg-Nielsen type	Supportive	Autosomal recessive

Mondo (1): hereditary palmoplantar keratoderma, Gamborg-Nielsen type (MONDO:0009489)

Orphanet (1): Hereditary palmoplantar keratoderma, Gamborg-Nielsen type (Orphanet:86923)

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST001642_1	Vaspin levels	4.000000e-41
GCST001762_212	Obesity-related traits	3.000000e-06
GCST001762_335	Obesity-related traits	7.000000e-06
GCST001762_624	Obesity-related traits	1.000000e-06
GCST001762_859	Obesity-related traits	3.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004915	vaspin measurement
EFO:0005106	body composition measurement
EFO:0005187	C-peptide measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C565454	Keratoderma, Palmoplantar, Norrbotten Recessive Type (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation, increases mutagenesis	2
sodium arsenate	decreases expression, increases abundance	1
sodium arsenite	affects methylation	1
hydroquinone	increases expression	1
benazol P	affects expression	1
abrine	increases expression	1
Arsenic	decreases expression, increases abundance	1
Urethane	decreases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	decreases methylation	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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