SERPINA12

protein-coding

serpin family A member 12, the group of Serpin peptidase inhibitors

Gene summary

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 obsolete extracellular space. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_001382267.1

Inheritance

—

ClinVar variants

P:1U:68B:10

Top phenotype

Hereditary palmoplantar keratoderma, Gamborg-Nielsen type

gnomAD constraint

pLI —, LoF o/e 0.89

Max pathogenic AF

—

Genomic locus

chr14:94,487,274-94,517,844

External References & Databases

Ensembl (ENSG00000165953)

Transcript & Mutation Effects

hg38 • Region Span ~30.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SERPINA12 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 68

not providedTotal: 7

Hereditary palmoplantar keratoderma, Gamborg-Nielsen typeTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001382267.1. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar		2 clinvar	3
missense			67 clinvar	5 clinvar	2 clinvar	74
nonsense	1 clinvar			1 clinvar		2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	1	0	68	6	4	79

Highest pathogenic variant AF is 0.0000024787048

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 12 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001382267.1	RefSeq	NP_001369196.1	4	MANE Select
ENST00000677451.1	Ensembl	ENSP00000503935.1	4	MANE Select
NM_001304461.2	RefSeq	NP_001291390.1	4	Standard
NM_173850.4	RefSeq	NP_776249.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

negative regulation of endopeptidase activity
positive regulation of phosphatidylinositol 3-kinase signaling
negative regulation of gluconeogenesis
positive regulation of insulin receptor signaling pathway
negative regulation of lipid biosynthetic process

Molecular Function

serine-type endopeptidase inhibitor activity

Cellular Component

extracellular space
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000341228
Coding exons: 4
Length: 30571
Individuals with no LoFs: 124288
Homozygous LoFs: 5
Heterozygous LoFs: 1455
Defined: 125748
p: 0.00582

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.04	278	233	1.19	0.0000126	2757
Missense (PolyPhen)		88	70.607	1.2463		936
Synonymous	-0.453	103	97.3	1.06	0.00000611	796
Loss of Function	0.340	10	11.2	0.891	4.76e-7	149

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0022	0.0022	notable
Latino/Admixed American	0.0029	0.0028	notable
Ashkenazi Jewish	0.00021	0.00020	rare
East Asian	0.0069	0.0069	notable
Finnish	0.012	0.012	notable
European (Non-Finnish)	0.0081	0.0079	notable
South Asian	0.00082	0.00078	rare
Other	0.0046	0.0044	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Adipokine that modulates insulin action by specifically inhibiting its target protease KLK7 in white adipose tissues. {ECO:0000269|PubMed:16030142}.;

Recessive Scores

pRec: 0.122

Intolerance Scores

RVIS EVS: 1.42
RVIS percentile EVS: 94.92

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.206

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium