NKD2

protein-coding

NKD inhibitor of WNT signaling pathway 2, the group of EF-hand domain containing

Gene summary

This gene encodes a member of a family of proteins that function as negative regulators of Wnt receptor signaling through interaction with Dishevelled family members. The encoded protein participates in the delivery of transforming growth factor alpha-containing vesicles to the cell membrane. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Aug 2012]

MANE transcript

NM_033120.4

Inheritance

—

ClinVar variants

U:105B:16

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.02

Max pathogenic AF

—

Genomic locus

chr5:1,008,802-1,038,943

External References & Databases

Ensembl (ENSG00000145506)

Transcript & Mutation Effects

hg38 • Region Span ~30.1 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 NKD2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 108

not providedTotal: 9

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_033120.4. 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			2 clinvar	4 clinvar		6
missense			100 clinvar	9 clinvar	3 clinvar	112
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	105	13	3	121

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 28 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_033120.4	RefSeq	NP_149111.1	10	MANE Select
ENST00000296849.10	Ensembl	ENSP00000296849.5	10	MANE Select
NM_001271082.2	RefSeq	NP_001258011.1	10	Standard
ENST00000274150.4	Ensembl	ENSP00000274150.4	10	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
nkd2a	Danio rerio	Structure: organizer inducing center Quality: increased width abnormal

Gene / Model

Organism

Observed Phenotype

nkd2a

Danio rerio

Structure: organizer inducing center

Quality: increased width

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Wnt signaling pathway - Homo sapiens (human)
Wnt Signaling Pathway and Pluripotency
Wnt Signaling Pathway
wnt signaling pathway
segmentation clock

Biological Process

exocytosis
positive regulation of protein processing
Wnt signaling pathway
negative regulation of Wnt signaling pathway
positive regulation of proteasomal ubiquitin-dependent protein catabolic process

Molecular Function

calcium ion binding
protein binding
growth factor binding
ubiquitin protein ligase binding
myosin heavy chain binding

Cellular Component

cytoplasm
plasma membrane
basolateral plasma membrane
lateral plasma membrane
cytoplasmic vesicle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000296849
Coding exons: 10
Length: 30115
Individuals with no LoFs: 125262
Homozygous LoFs: 0
Heterozygous LoFs: 46
Defined: 125308
p: 0.000184

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.0981	277	272	1.02	0.0000186	2872
Missense (PolyPhen)		94	89.211	1.0537		941
Synonymous	0.386	118	123	0.956	0.00000927	896
Loss of Function	-0.0686	18	17.7	1.02	8.32e-7	235

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	0.00033	0.00033	rare
Finnish	0.00020	0.00018	rare
European (Non-Finnish)	0.00017	0.00016	rare
South Asian	0.00038	0.00036	rare
Other	0.00054	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Cell autonomous antagonist of the canonical Wnt signaling pathway. May activate a second Wnt signaling pathway that controls planar cell polarity (By similarity). Required for processing of TGFA and for targeting of TGFA to the basolateral membrane of polarized epithelial cells. {ECO:0000250, ECO:0000269|PubMed:15064403, ECO:0000269|PubMed:17553928}.;

Recessive Scores

pRec: 0.102

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.840

Gene Damage Prediction

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