CTRC

protein-coding

chymotrypsin C

Gene summary

This gene encodes a member of the peptidase S1 family. The encoded protein is a serum calcium-decreasing factor that has chymotrypsin-like protease activity. Alternatively spliced transcript variants have been observed, but their full-length nature has not been determined. [provided by RefSeq, Jul 2008]

MANE transcript

NM_007272.3

Inheritance

ClinVar variants

P:36U:430B:244

Top phenotype

hereditary chronic pancreatitis

gnomAD constraint

pLI —, LoF o/e 1.15

Max pathogenic AF

—

Genomic locus

chr1:15,438,442-15,449,242

External References & Databases

Ensembl (ENSG00000162438)

Transcript & Mutation Effects

hg38 • Region Span ~10.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

hereditary chronic pancreatitisSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0008185

Submitter: Labcorp Genetics (formerly Invitae)

hereditary chronic pancreatitisDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0008185

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CTRC variants in ClinVar

7 Conditions Cataloged

Hereditary pancreatitisTotal: 772

not providedTotal: 71

CTRC-related disorderTotal: 18

not specifiedTotal: 16

Pancreatitis, chronic, susceptibility toTotal: 3

Chronic pancreatitisTotal: 1

Multiple congenital anomalies/dysmorphic syndrome-intellectual disabilityTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_007272.3. 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		1 clinvar	2 clinvar	217 clinvar	2 clinvar	222
missense		8 clinvar	417 clinvar	24 clinvar	1 clinvar	450
nonsense	3 clinvar	6 clinvar	2 clinvar			11
start loss		2 clinvar				2
frameshift	3 clinvar	8 clinvar	3 clinvar			14
splice donor/acceptor (+/-2bp)		5 clinvar	6 clinvar			11
Total	6	30	430	241	3	710

Highest pathogenic variant AF is 0.00029616486

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 5 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_007272.3	RefSeq	NP_009203.2	8	MANE Select
ENST00000375949.5	Ensembl	ENSP00000365116.4	8	MANE Select
ENST00000375943.6	Ensembl	ENSP00000365110.2	3	Standard
ENST00001143575.1	Ensembl	ENSP00000810611.1	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Cobalamin (Cbl, vitamin B12) transport and metabolism
Metabolism
Metabolism of water-soluble vitamins and cofactors
Metabolism of vitamins and cofactors
Urokinase-type plasminogen activator (uPA) and uPAR-mediated signaling

Biological Process

proteolysis
cobalamin metabolic process

Molecular Function

serine-type endopeptidase activity
protein binding
peptidase activity

Cellular Component

extracellular region

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000375949
Coding exons: 8
Length: 10803
Individuals with no LoFs: 125686
Homozygous LoFs: 0
Heterozygous LoFs: 62
Defined: 125748
p: 0.000247

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.134	168	163	1.03	0.0000114	1740
Missense (PolyPhen)		74	68.744	1.0765		733
Synonymous	-0.198	72	69.9	1.03	0.00000531	535
Loss of Function	-0.521	17	14.8	1.15	7.38e-7	159

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00049	0.00049	rare
Latino/Admixed American	0.00052	0.00052	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00022	0.00022	rare
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.00011	0.00011	rare
South Asian	0.00036	0.00036	rare
Other	0.0011	0.0011	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Regulates activation and degradation of trypsinogens and procarboxypeptidases by targeting specific cleavage sites within their zymogen precursors. Has chymotrypsin-type protease activity and hypocalcemic activity. {ECO:0000269|PubMed:23430245}.;

Intolerance Scores

LoFtool: 0.280
RVIS EVS: 0.02
RVIS percentile EVS: 55.22

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.271

Gene Damage Prediction

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