WLS

protein-coding

Wnt ligand secretion mediator, the group of MicroRNA protein coding host genes

Gene summary

Enables Wnt-protein binding activity and identical protein binding activity. Involved in Wnt protein secretion; intracellular protein transport; and positive regulation of cell communication. Located in several cellular components, including Golgi apparatus; early endosome; and endoplasmic reticulum membrane. Implicated in Zaki syndrome. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

C1orf139
GPR177

MANE transcript

NM_024911.7

Inheritance

ClinVar variants

P:5U:88B:9

Top phenotype

Zaki syndrome

gnomAD constraint

pLI —, LoF o/e 0.3

Max pathogenic AF

—

Genomic locus

chr1:68,098,473-68,233,120

External References & Databases

Ensembl (ENSG00000116729)

Transcript & Mutation Effects

hg38 • Region Span ~134.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Zaki syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0859209

Submitter: PanelApp Australia

Zaki syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0859209

Submitter: Labcorp Genetics (formerly Invitae)

Zaki syndromeLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0859209

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to WLS variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 72

Zaki syndromeTotal: 14

not providedTotal: 10

WLS-related disorderTotal: 6

WLS syndromeTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_024911.7. 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				8 clinvar		8
missense	1 clinvar	4 clinvar	83 clinvar	1 clinvar		89
nonsense			2 clinvar			2
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	1	4	88	9	0	102

Highest pathogenic variant AF is 0.000052667714

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 31 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_024911.7	RefSeq	NP_079187.3	12	MANE Select
ENST00000262348.9	Ensembl	ENSP00000262348.4	12	MANE Select
NM_001002292.4	RefSeq	NP_001002292.3	12	Standard
NM_001193334.1	RefSeq	NP_001180263.1	11	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
wls	Danio rerio	Structure: chondrocyte Quality: disorganized abnormal

Gene / Model

Organism

Observed Phenotype

wls

Danio rerio

Structure: chondrocyte

Quality: disorganized

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Signaling by WNT
Signal Transduction
WNT ligand biogenesis and trafficking

Biological Process

mesoderm formation
intracellular protein transport
anterior/posterior axis specification
Wnt signaling pathway
positive regulation of Wnt signaling pathway

Molecular Function

protein binding
Wnt-protein binding
mu-type opioid receptor binding

Cellular Component

Golgi membrane
early endosome
endoplasmic reticulum membrane
Golgi apparatus
trans-Golgi network

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000354777
Coding exons: 12
Length: 134662
Individuals with no LoFs: 125727
Homozygous LoFs: 0
Heterozygous LoFs: 21
Defined: 125748
p: 0.0000835

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.603	295	326	0.906	0.0000181	3652
Missense (PolyPhen)		86	121.47	0.70797		1390
Synonymous	0.0102	119	119	0.999	0.00000717	991
Loss of Function	3.33	8	26.5	0.302	0.00000142	275

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00017	0.00017	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.00018	0.00018	rare
European (Non-Finnish)	0.000053	0.000053	rare
South Asian	0.000098	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Regulates Wnt proteins sorting and secretion in a feedback regulatory mechanism. This reciprocal interaction plays a key role in the regulation of expression, subcellular location, binding and organelle-specific association of Wnt proteins. Plays also an important role in establishment of the anterior-posterior body axis formation during development (By similarity). {ECO:0000250, ECO:0000269|PubMed:16678095, ECO:0000269|PubMed:16678096}.;

Recessive Scores

pRec: 0.173

Intolerance Scores

LoFtool: 0.443
RVIS EVS: -0.6
RVIS percentile EVS: 18.06

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.114

Gene Damage Prediction

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