CALML5

protein-coding

calmodulin like 5, the group of EF-hand domain containing

Gene summary

This gene encodes a novel calcium binding protein expressed in the epidermis and related to the calmodulin family of calcium binding proteins. Functional studies with recombinant protein demonstrate it does bind calcium and undergoes a conformational change when it does so. Abundant expression is detected only in reconstructed epidermis and is restricted to differentiating keratinocytes. In addition, it can associate with transglutaminase 3, shown to be a key enzyme in the terminal differentiation of keratinocytes. [provided by RefSeq, Jul 2008]

MANE transcript

NM_017422.5

Inheritance

—

ClinVar variants

U:17B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e —

Max pathogenic AF

—

Genomic locus

chr10:5,498,697-5,499,570

External References & Databases

Ensembl (ENSG00000178372)

Transcript & Mutation Effects

hg38 • Region Span ~0.9 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 CALML5 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 19

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_017422.5. 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						0
missense			17 clinvar	2 clinvar		19
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	17	2	0	19

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 2 of 2 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_017422.5	RefSeq	NP_059118.2	1	MANE Select
ENST00000380332.5	Ensembl	ENSP00000369689.3	1	MANE Select

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Inflammatory mediator regulation of TRP channels - Homo sapiens (human)
Aldosterone synthesis and secretion - Homo sapiens (human)
Oxytocin signaling pathway - Homo sapiens (human)
Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human)
Pertussis - Homo sapiens (human)

Biological Process

signal transduction
epidermis development
calcium-mediated signaling
neutrophil degranulation
regulation of catalytic activity

Molecular Function

calcium ion binding

Cellular Component

extracellular region
ficolin-1-rich granule lumen

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000380332
Coding exons: 1
Length: 876

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.720	85	106	0.803	0.00000793	938
Missense (PolyPhen)		23	31.408	0.7323		364
Synonymous	0.0405	54	54.4	0.993	0.00000512	288
Loss of Function

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Binds calcium. May be involved in terminal differentiation of keratinocytes.;

Recessive Scores

pRec: 0.0872

Intolerance Scores

LoFtool: 0.416
RVIS EVS: 0.64
RVIS percentile EVS: 83.78

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.381

Gene Damage Prediction

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