CHST8

protein-coding

carbohydrate sulfotransferase 8, the group of Sulfotransferases, membrane bound

Gene summary

The protein encoded by this gene belongs to the sulfotransferase 2 family. It is predominantly expressed in the pituitary gland, and is localized to the golgi membrane. This protein catalyzes the transfer of sulfate to position 4 of non-reducing N-acetylgalactosamine (GalNAc) residues in both N-glycans and O-glycans. It is responsible for sulfation of GalNAc on luteinizing hormone (LH), which is required for production of the sex hormones. Mice lacking this enzyme, exhibit increased levels of circulating LH, and precocious sexual maturation of both male and female mice. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Aug 2011]

MANE transcript

NM_001127895.2

Inheritance

AR, AD

ClinVar variants

U:68B:17

Top phenotype

Peeling skin syndrome 3

gnomAD constraint

pLI —, LoF o/e 0.62

Max pathogenic AF

—

Genomic locus

chr19:33,621,953-33,773,509

External References & Databases

Ensembl (ENSG00000124302)

Transcript & Mutation Effects

hg38 • Region Span ~151.6 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

peeling skin syndrome type ALIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0014555

Submitter: G2P

peeling skin syndrome type ASUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0014555

Submitter: Orphanet

Clinical Genomic Database (CGD)

Peeling skin syndrome 3AD

Manifestation: Dermatologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 22289416

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CHST8 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 77

not providedTotal: 7

CHST8-related disorderTotal: 7

Peeling skin syndrome type ATotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001127895.2. 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				4 clinvar	3 clinvar	7
missense			68 clinvar	10 clinvar		78
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	68	14	3	85

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 27 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001127895.2	RefSeq	NP_001121367.1	3	MANE Select
ENST00000650847.1	Ensembl	ENSP00000499084.1	3	MANE Select
NM_001127896.2	RefSeq	NP_001121368.1	3	Standard
NM_022467.3	RefSeq	NP_071912.2	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Metapathway biotransformation Phase I and II
Post-translational protein modification
Reactions specific to the complex N-glycan synthesis pathway
N-glycan antennae elongation in the medial/trans-Golgi
Metabolism of proteins

Biological Process

sulfur compound metabolic process
central nervous system development
carbohydrate biosynthetic process
proteoglycan biosynthetic process
hormone biosynthetic process

Molecular Function

N-acetylgalactosamine 4-O-sulfotransferase activity

Cellular Component

Golgi membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000262622
Coding exons: 3
Length: 151554
Individuals with no LoFs: 125720
Homozygous LoFs: 0
Heterozygous LoFs: 27
Defined: 125747
p: 0.000107

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.01	266	316	0.840	0.0000239	2726
Missense (PolyPhen)		80	110.52	0.72387		939
Synonymous	0.967	125	140	0.896	0.0000105	900
Loss of Function	1.26	8	12.9	0.620	7.23e-7	124

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.00015	0.00014	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000058	0.000054	rare
Finnish	0.000047	0.000046	rare
European (Non-Finnish)	0.000099	0.000097	rare
South Asian	0.00017	0.00016	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Catalyzes the transfer of sulfate to position 4 of non- reducing N-acetylgalactosamine (GalNAc) residues in both N-glycans and O-glycans. Required for biosynthesis of glycoprotein hormones lutropin and thyrotropin, by mediating sulfation of their carbohydrate structures. Only active against terminal GalNAcbeta1,GalNAcbeta. Not active toward chondroitin. {ECO:0000269|PubMed:10988300, ECO:0000269|PubMed:11445554}.;
Disease: DISEASE: Peeling skin syndrome 3 (PSS3) [MIM:616265]: A form of peeling skin syndrome, a genodermatosis characterized by generalized, continuous shedding of the outer layers of the epidermis. Two main PSS subtypes have been suggested. Patients with non-inflammatory PSS (type A) manifest white scaling, with painless and easy removal of the skin, irritation when in contact with water, dust and sand, and no history of erythema, pruritis or atopy. Inflammatory PSS (type B) is associated with generalized erythema, pruritus and atopy. It is an ichthyosiform erythroderma characterized by lifelong patchy peeling of the entire skin with onset at birth or shortly after. Several patients have been reported with high IgE levels. PSS3 is characterized by generalized white scaling occurring over the upper and lower extremities. Symptoms start during the second half of the first decade of life. {ECO:0000269|PubMed:22289416}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.110

Intolerance Scores

LoFtool: 0.629
RVIS EVS: -0.32
RVIS percentile EVS: 31.69

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.563

Gene Damage Prediction

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