SULT2B1

protein-coding

sulfotransferase family 2B member 1, the group of Sulfotransferases, cytosolic

Gene summary

Sulfotransferase enzymes catalyze the sulfate conjugation of many hormones, neurotransmitters, drugs, and xenobiotic compounds. These cytosolic enzymes are different in their tissue distributions and substrate specificities. The gene structure (number and length of exons) is similar among family members. This gene sulfates dehydroepiandrosterone but not 4-nitrophenol, a typical substrate for the phenol and estrogen sulfotransferase subfamilies. Two alternatively spliced variants that encode different isoforms have been described. [provided by RefSeq, Jul 2008]

MANE transcript

NM_177973.2

Inheritance

ClinVar variants

P:7U:59B:28

Top phenotype

Ichthyosis, congenital, autosomal recessive 14

gnomAD constraint

pLI —, LoF o/e 0.21

Max pathogenic AF

—

Genomic locus

chr19:48,552,172-48,599,425

External References & Databases

Ensembl (ENSG00000088002)

Transcript & Mutation Effects

hg38 • Region Span ~47.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

ichthyosis, congenital, autosomal recessive 14LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0033091

Submitter: Ambry Genetics

ichthyosis, congenital, autosomal recessive 14STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0033091

Submitter: Labcorp Genetics (formerly Invitae)

ichthyosis, congenital, autosomal recessive 14STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0033091

Submitter: Genomics England PanelApp

ichthyosis, congenital, autosomal recessive 14STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0033091

Submitter: G2P

lamellar ichthyosisSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0017778

Submitter: Orphanet

ichthyosis, congenital, autosomal recessive 14STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0033091

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Ichthyosis, congenital, autosomal recessive 14AR

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: 28575648

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SULT2B1 variants in ClinVar

7 Conditions Cataloged

Inborn genetic diseasesTotal: 56

not providedTotal: 41

SULT2B1-related disorderTotal: 9

Ichthyosis, congenital, autosomal recessive 14Total: 7

not specifiedTotal: 5

Autosomal recessive congenital ichthyosis 2Total: 3

Autosomal recessive congenital ichthyosis 1Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_177973.2. 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				17 clinvar		17
missense	2 clinvar	2 clinvar	58 clinvar	7 clinvar	4 clinvar	73
nonsense	1 clinvar					1
start loss						0
frameshift	1 clinvar					1
splice donor/acceptor (+/-2bp)	1 clinvar		1 clinvar			2
Total	5	2	59	24	4	94

Highest pathogenic variant AF is 0.000023569839

Loading ClinVar variants...

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_177973.2	RefSeq	NP_814444.1	7	MANE Select
ENST00000201586.7	Ensembl	ENSP00000201586.2	7	MANE Select
NM_004605.2	RefSeq	NP_004596.2	6	Standard
ENST00000323090.4	Ensembl	ENSP00000312880.3	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Steroid hormone biosynthesis - Homo sapiens (human)
17-Beta Hydroxysteroid Dehydrogenase III Deficiency
Sulfate/Sulfite Metabolism
Sulfite oxidase deficiency
Androgen and Estrogen Metabolism

Biological Process

sulfate assimilation
steroid metabolic process
cholesterol metabolic process
negative regulation of cell population proliferation
positive regulation of epidermal cell differentiation

Molecular Function

nucleic acid binding
alcohol sulfotransferase activity
protein binding
cholesterol binding
steroid sulfotransferase activity

Cellular Component

nucleus
cytoplasm
endoplasmic reticulum
cytosol
intracellular membrane-bounded organelle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000201586
Coding exons: 7
Length: 47351
Individuals with no LoFs: 125738
Homozygous LoFs: 0
Heterozygous LoFs: 7
Defined: 125745
p: 0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.11	187	235	0.796	0.0000153	2367
Missense (PolyPhen)		49	74.923	0.654		800
Synonymous	0.132	99	101	0.983	0.00000741	685
Loss of Function	2.74	3	14.1	0.213	5.99e-7	164

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000038	0.000035	rare
South Asian	0.000034	0.000033	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfate conjugation of many hormones, neurotransmitters, drugs and xenobiotic compounds. Sulfonation increases the water solubility of most compounds, and therefore their renal excretion, but it can also result in bioactivation to form active metabolites. Sulfates hydroxysteroids like DHEA. Isoform 1 preferentially sulfonates cholesterol, and isoform 2 avidly sulfonates pregnenolone but not cholesterol. Plays a role in epidermal cholesterol metabolism and in the regulation of epidermal proliferation and differentiation (PubMed:28575648). {ECO:0000269|PubMed:12145317, ECO:0000269|PubMed:28575648, ECO:0000269|PubMed:9799594}.;

Recessive Scores

pRec: 0.576

Intolerance Scores

LoFtool: 0.0652
RVIS EVS: 0.62
RVIS percentile EVS: 83.36

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.998

Gene Damage Prediction

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