KAZALD1

protein-coding

Kazal type serine peptidase inhibitor domain 1, the group of I-set domain containing

Gene summary

This gene encodes a secreted member of the insulin growth factor-binding protein (IGFBP) superfamily. The protein contains an insulin growth factor-binding domain in its N-terminal region, a Kazal-type serine protease inhibitor and follistatin-like domain in its central region, and an immunoglobulin-like domain in its C-terminal region. Studies of the mouse ortholog suggest that this protein may function in bone development and bone regeneration. This gene is hypomethylated and over-expressed in high-grade glioma compared to low-grade glioma, and thus the hypomethylated gene may be associated with cell proliferation and the shorter survival of patients with high-grade glioma. It is also one of numerous genes found to be deleted in a novel 5.54 Mb interstitial deletion, which is associated with multiple congenital anomalies. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

MANE transcript

NM_030929.5

Inheritance

—

ClinVar variants

U:64B:7

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.87

Max pathogenic AF

—

Genomic locus

chr10:101,061,989-101,068,131

External References & Databases

Ensembl (ENSG00000107821)

Transcript & Mutation Effects

hg38 • Region Span ~6.1 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 KAZALD1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 61

not providedTotal: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_030929.5. 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	2
missense			63 clinvar	2 clinvar	2 clinvar	67
nonsense				1 clinvar		1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	64	3	4	71

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 16 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_030929.5	RefSeq	NP_112191.2	4	MANE Select
ENST00000370200.6	Ensembl	ENSP00000359219.6	4	MANE Select
NM_001319303.2	RefSeq	NP_001306232.1	4	Standard
ENST00000891380.1	Ensembl	ENSP00000561439.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

ossification
regulation of cell growth
multicellular organism development
cell differentiation
extracellular matrix organization

Molecular Function

insulin-like growth factor binding

Cellular Component

interstitial matrix

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000370200
Coding exons: 4
Length: 6291
Individuals with no LoFs: 125676
Homozygous LoFs: 0
Heterozygous LoFs: 63
Defined: 125739
p: 0.000251

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.122	164	168	0.973	0.00000824	1900
Missense (PolyPhen)		80	69.046	1.1586		782
Synonymous	0.326	70	73.6	0.952	0.00000365	656
Loss of Function	0.418	10	11.5	0.867	4.97e-7	115

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0.0024	0.0024	notable
East Asian	0.00011	0.00011	rare
Finnish	0.00029	0.00014	rare
European (Non-Finnish)	0.00025	0.00022	rare
South Asian	0.00013	0.00013	rare
Other	0.00038	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in the proliferation of osteoblasts during bone formation and bone regeneration. Promotes matrix assembly (By similarity). {ECO:0000250}.;

Intolerance Scores

LoFtool: 0.561
RVIS EVS: 0.9
RVIS percentile EVS: 89.39

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0401

Gene Damage Prediction

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