CHIT1

protein-coding

chitinase 1, the group of Chitinases

Gene summary

Chitotriosidase is secreted by activated human macrophages and is markedly elevated in plasma of Gaucher disease patients. The expression of chitotriosidase occurs only at a late stage of differentiation of monocytes to activated macrophages in culture. Human macrophages can synthesize a functional chitotriosidase, a highly conserved enzyme with a strongly regulated expression. This enzyme may play a role in the degradation of chitin-containing pathogens. Several alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Jan 2012]

MANE transcript

NM_003465.3

Inheritance

ClinVar variants

U:71B:125

Top phenotype

Chitotriosidase deficiency

gnomAD constraint

pLI —, LoF o/e 0.95

Max pathogenic AF

—

Genomic locus

chr1:203,212,827-203,273,641

External References & Databases

Ensembl (ENSG00000133063)

Transcript & Mutation Effects

hg38 • Region Span ~60.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

Clinical Genomic Database (CGD)

Chitotriosidase deficiencyAR

Manifestation: Biochemical

Intervention: General

Rationale: Variants may have implications for monitoring (including related to therapy) in Gaucher disease; Testing relevant to Gaucher disease, if necessary, would be tested as part of care

Refs: 8132768; 9748235; 16972172; 17464953; 17693102; 15900564; 15528158; 22959626

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CHIT1 variants in ClinVar

3 Conditions Cataloged

Chitotriosidase deficiencyTotal: 164

not specifiedTotal: 93

not providedTotal: 26

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003465.3. 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			3 clinvar	40 clinvar	4 clinvar	47
missense			66 clinvar	52 clinvar	27 clinvar	145
nonsense			1 clinvar			1
start loss						0
frameshift					1 clinvar	1
splice donor/acceptor (+/-2bp)			1 clinvar		1 clinvar	2
Total	0	0	71	92	33	196

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 45 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003465.3	RefSeq	NP_003456.1	11	MANE Select
ENST00000367229.6	Ensembl	ENSP00000356198.1	11	MANE Select
NM_001256125.2	RefSeq	NP_001243054.2	10	Standard
ENST00000255427.7	Ensembl	ENSP00000255427.3	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Amino sugar and nucleotide sugar metabolism - Homo sapiens (human)
Sialuria or French Type Sialuria
Sialuria or French Type Sialuria
Amino Sugar Metabolism
G(M2)-Gangliosidosis: Variant B, Tay-sachs disease

Biological Process

polysaccharide catabolic process
chitin catabolic process
immune response
response to bacterium
neutrophil degranulation

Molecular Function

hydrolase activity, hydrolyzing O-glycosyl compounds
chitinase activity
chitin binding
endochitinase activity

Cellular Component

extracellular region
extracellular space
lysosome
specific granule lumen
tertiary granule lumen

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000367229
Coding exons: 11
Length: 60815
Individuals with no LoFs: 123431
Homozygous LoFs: 60
Heterozygous LoFs: 2257
Defined: 125748
p: 0.00926

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.191	265	256	1.03	0.0000153	3037
Missense (PolyPhen)		104	94.746	1.0977		1236
Synonymous	-0.856	115	104	1.11	0.00000655	903
Loss of Function	0.222	24	25.2	0.952	0.00000120	279

Population LoF Frequency

Population	CAF	p-value	Status
African	0.085	0.085	notable
Latino/Admixed American	0.0055	0.0055	notable
Ashkenazi Jewish	0.0065	0.0066	notable
East Asian	0.00027	0.00027	rare
Finnish	0.0062	0.0062	notable
European (Non-Finnish)	0.0043	0.0043	notable
South Asian	0.0026	0.0026	notable
Other	0.0064	0.0062	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Degrades chitin, chitotriose and chitobiose. May participate in the defense against nematodes and other pathogens. Isoform 3 has no enzymatic activity. {ECO:0000269|PubMed:7592832, ECO:0000269|PubMed:7836450}.;

Recessive Scores

pRec: 0.264

Intolerance Scores

LoFtool: 0.923
RVIS EVS: 1.05
RVIS percentile EVS: 91.32

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.896

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High