STX16

protein-coding

syntaxin 16, the group of Syntaxins

Gene summary

This gene encodes a protein that is a member of the syntaxin or t-SNARE (target-SNAP receptor) family. These proteins are found on cell membranes and serve as the targets for V-SNARES (vesicle-SNAP receptors) permitting specific synaptic vesicle docking and fusion. A microdeletion in the region of chromosome 20 where this gene is located has been associated with pseudohypoparathyroidism type Ib. Multiple transcript variants have been found for this gene. Read-through transcription also exists between this gene and the neighboring downstream aminopeptidase-like 1 (NPEPL1) gene. [provided by RefSeq, Mar 2011]

MANE transcript

NM_001001433.3

Inheritance

ClinVar variants

P:3U:107B:40

Top phenotype

Pseudohypoparathyroidism, type IB

gnomAD constraint

pLI —, LoF o/e 0.21

Max pathogenic AF

—

Genomic locus

chr20:58,651,272-58,679,526

External References & Databases

Ensembl (ENSG00000124222)

Transcript & Mutation Effects

hg38 • Region Span ~28.3 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

pseudohypoparathyroidism type 1BSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0011301

Submitter: Orphanet

pseudohypoparathyroidism type 1BSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0011301

Submitter: Ambry Genetics

pseudohypoparathyroidism type 1BSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0011301

Submitter: Labcorp Genetics (formerly Invitae)

pseudohypoparathyroidism type 1BSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0011301

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Pseudohypoparathyroidism, type IBAD

Manifestation: Endocrine; Renal

Intervention: Endocrine; Renal

Rationale: Complications such as osteitis fibrosa cystica may be effectively treated with calcium and vitamin D therapy

Refs: 15537666; 17595244; 18626245; 20960161; 20538864; 21752878

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to STX16 variants in ClinVar

5 Conditions Cataloged

Pseudohypoparathyroidism type 1BTotal: 88

not providedTotal: 79

Inborn genetic diseasesTotal: 46

STX16-related disorderTotal: 7

not specifiedTotal: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001001433.3. 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			5 clinvar	24 clinvar	3 clinvar	32
missense			95 clinvar	11 clinvar	1 clinvar	107
nonsense					1 clinvar	1
start loss			1 clinvar			1
frameshift			5 clinvar			5
splice donor/acceptor (+/-2bp)	3 clinvar		1 clinvar			4
Total	3	0	107	35	5	150

Highest pathogenic variant AF is 0.0000027477283

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 41 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001001433.3	RefSeq	NP_001001433.1	9	MANE Select
ENST00000371141.8	Ensembl	ENSP00000360183.4	9	MANE Select
NM_001134772.3	RefSeq	NP_001128244.1	8	Standard
NM_001134773.3	RefSeq	NP_001128245.1	9	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
stx16	Danio rerio	Structure: whole organism Quality: increased curvature abnormal

Gene / Model

Organism

Observed Phenotype

stx16

Danio rerio

Structure: whole organism

Quality: increased curvature

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

SNARE interactions in vesicular transport - Homo sapiens (human)
Nicotine Pathway (Dopaminergic Neuron), Pharmacodynamics
Ectoderm Differentiation
Vesicle-mediated transport
Membrane Trafficking

Biological Process

intracellular protein transport
vesicle fusion
retrograde transport, endosome to Golgi
vesicle docking
Golgi ribbon formation

Molecular Function

SNARE binding
SNAP receptor activity
protein binding
syntaxin binding

Cellular Component

Golgi membrane
cytoplasm
Golgi apparatus
trans-Golgi network
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000371141
Coding exons: 9
Length: 28255
Individuals with no LoFs: 125738
Homozygous LoFs: 0
Heterozygous LoFs: 10
Defined: 125748
p: 0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.952	160	198	0.809	0.0000115	2126
Missense (PolyPhen)		35	46.14	0.75855		540
Synonymous	0.435	70	74.8	0.936	0.00000435	627
Loss of Function	3.19	4	19.0	0.210	0.00000102	208

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000026	0.000026	rare
South Asian	0.000098	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: SNARE involved in vesicular transport from the late endosomes to the trans-Golgi network. {ECO:0000269|PubMed:18195106}.;

Recessive Scores

pRec: 0.0823

Intolerance Scores

LoFtool: 0.632
RVIS EVS: -0.25
RVIS percentile EVS: 35.99

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.863

Gene Damage Prediction

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