CRIM1

protein-coding

cysteine rich transmembrane BMP regulator 1, the group of Cysteine rich transmembrane BMP regulators

Gene summary

This gene encodes a transmembrane protein containing six cysteine-rich repeat domains and an insulin-like growth factor-binding domain. The encoded protein may play a role in tissue development though interactions with members of the transforming growth factor beta family, such as bone morphogenetic proteins. [provided by RefSeq, Nov 2010]

Previous symbols:

MANE transcript

NM_016441.3

Inheritance

ClinVar variants

U:201B:40

Top phenotype

colobomatous macrophthalmia-microcornea syndrome

gnomAD constraint

pLI —, LoF o/e 0.12

Max pathogenic AF

—

Genomic locus

chr2:36,355,778-36,551,135

External References & Databases

Ensembl (ENSG00000150938)

Transcript & Mutation Effects

hg38 • Region Span ~195.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

colobomatous macrophthalmia-microcornea syndromeSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0011239

Submitter: Orphanet

colobomatous macrophthalmia-microcornea syndromeLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0011239

Submitter: Labcorp Genetics (formerly Invitae)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CRIM1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 177

CRIM1-related disorderTotal: 27

not providedTotal: 24

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_016441.3. 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			15 clinvar	18 clinvar	5 clinvar	38
missense			173 clinvar	13 clinvar	4 clinvar	190
nonsense			4 clinvar			4
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			8 clinvar			8
Total	0	0	201	31	9	241

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 48 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_016441.3	RefSeq	NP_057525.1	17	MANE Select
ENST00000280527.7	Ensembl	ENSP00000280527.2	17	MANE Select
ENST00000413985.1	Ensembl	ENSP00000403120.1	4	Standard
ENST00000426856.1	Ensembl	ENSP00000407636.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

EGFR1

Biological Process

regulation of cell growth
nervous system development
negative regulation of endopeptidase activity
insulin-like growth factor receptor signaling pathway

Molecular Function

serine-type endopeptidase inhibitor activity
insulin-like growth factor-activated receptor activity
insulin-like growth factor binding
PDZ domain binding

Cellular Component

extracellular region
plasma membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000280527
Coding exons: 17
Length: 195210
Individuals with no LoFs: 125736
Homozygous LoFs: 0
Heterozygous LoFs: 12
Defined: 125748
p: 0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.194	587	600	0.978	0.0000349	6794
Missense (PolyPhen)		346	383.26	0.90278		4341
Synonymous	-2.84	291	235	1.24	0.0000147	1970
Loss of Function	5.75	6	49.8	0.120	0.00000237	612

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000088	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000071	0.000053	rare
South Asian	0.000034	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May play a role in CNS development by interacting with growth factors implicated in motor neuron differentiation and survival. May play a role in capillary formation and maintenance during angiogenesis. Modulates BMP activity by affecting its processing and delivery to the cell surface. {ECO:0000269|PubMed:12464430, ECO:0000269|PubMed:12805376}.;

Intolerance Scores

LoFtool: 0.249
RVIS EVS: -1.1
RVIS percentile EVS: 6.93

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.964

Gene Damage Prediction

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