SPINK6

protein-coding

serine peptidase inhibitor Kazal type 6, the group of Serine peptidase inhibitors, Kazal type

Gene summary

The protein encoded by this gene is a Kazal-type serine protease inhibitor that acts on kallikrein-related peptidases in the skin. Two transcript variants the same protein have been found for this gene. [provided by RefSeq, Aug 2010]

MANE transcript

NM_205841.4

Inheritance

—

ClinVar variants

U:14

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.69

Max pathogenic AF

—

Genomic locus

chr5:148,202,794-148,215,137

External References & Databases

Ensembl (ENSG00000178172)

Transcript & Mutation Effects

hg38 • Region Span ~12.3 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 SPINK6 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 13

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_205841.4. 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			1
missense			13 clinvar			13
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	14	0	0	14

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 6 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_205841.4	RefSeq	NP_995313.2	4	MANE Select
ENST00000325630.3	Ensembl	ENSP00000324870.2	4	MANE Select
NM_001195290.2	RefSeq	NP_001182219.1	4	Standard
ENST00000514389.5	Ensembl	ENSP00000421119.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Keratinization
Developmental Biology
Formation of the cornified envelope

Biological Process

cornification
negative regulation of serine-type endopeptidase activity

Molecular Function

serine-type endopeptidase inhibitor activity

Cellular Component

extracellular region

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000325630
Coding exons: 4
Length: 12344
Individuals with no LoFs: 125721
Homozygous LoFs: 0
Heterozygous LoFs: 21
Defined: 125742
p: 0.0000835

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.376	48	41.2	1.17	0.00000190	516
Missense (PolyPhen)		21	18.456	1.1378		220
Synonymous	0.658	11	14.1	0.778	6.10e-7	142
Loss of Function	-1.39	8	4.73	1.69	1.99e-7	60

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000080	0.000079	rare
South Asian	0.00027	0.00026	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Serine protease inhibitor selective for kallikreins. Efficiently inhibits KLK4, KLK5, KLK6, KLK7, KLK12, KLK13 and KLK14. Doesn't inhibit KLK8. {ECO:0000269|PubMed:20667819, ECO:0000269|PubMed:21439340}.;

Intolerance Scores

LoFtool: 0.750
RVIS EVS: 0.52
RVIS percentile EVS: 80.46

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0861

Gene Damage Prediction

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