KEL

protein-coding

Kell metallo-endopeptidase (Kell blood group), the group of Blood group antigens|CD molecules|M13 metallopeptidases

Gene summary

This gene encodes a type II transmembrane glycoprotein that is the highly polymorphic Kell blood group antigen. The Kell glycoprotein links via a single disulfide bond to the XK membrane protein that carries the Kx antigen. The encoded protein contains sequence and structural similarity to members of the neprilysin (M13) family of zinc endopeptidases. [provided by RefSeq, Jul 2008]

MANE transcript

NM_000420.3

Inheritance

ClinVar variants

P:2U:108B:15

Top phenotype

Blood group, Kell system

gnomAD constraint

pLI —, LoF o/e 0.83

Max pathogenic AF

—

Genomic locus

chr7:142,941,114-142,962,363

External References & Databases

Ensembl (ENSG00000197993)

Transcript & Mutation Effects

hg38 • Region Span ~21.2 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

Clinical Genomic Database (CGD)

Blood group, Kell systemBG

Manifestation: Hematologic

Intervention: Hematologic

Rationale: Variants associated with a blood group may be important in specific situations (eg, related to transfusion)

Refs: 7849312; 11134029; 12842980; 15373667; 16423827

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to KEL variants in ClinVar

9 Conditions Cataloged

not specifiedTotal: 94

not providedTotal: 15

KEL-related disorderTotal: 7

Kell blood group systemTotal: 7

Vein of Galen aneurysmal malformationTotal: 5

Vein of Galen arteriovenous malformationsTotal: 1

KELL-NULL PHENOTYPETotal: 1

Hartsfield-Bixler-Demyer syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000420.3. 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	3 clinvar	3 clinvar	7
missense			104 clinvar	8 clinvar	1 clinvar	113
nonsense			3 clinvar			3
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)	2 clinvar					2
Total	2	0	108	11	4	125

Highest pathogenic variant AF is 0.000001368122

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 11 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000420.3	RefSeq	NP_000411.1	19	MANE Select
ENST00000355265.7	Ensembl	ENSP00000347409.2	19	MANE Select
ENST00000460479.2	Ensembl	ENSP00000418886.2	4	Standard
ENST00000467543.6	Ensembl	ENSP00000420011.2	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Signaling by GPCR
Signal Transduction
Peptide ligand-binding receptors
Class A/1 (Rhodopsin-like receptors)
GPCR ligand binding

Biological Process

proteolysis
cellular calcium ion homeostasis
regulation of cell size
cellular magnesium ion homeostasis
regulation of axon diameter

Molecular Function

metalloendopeptidase activity
protein binding
metal ion binding

Cellular Component

plasma membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000355265
Coding exons: 19
Length: 21568
Individuals with no LoFs: 125555
Homozygous LoFs: 2
Heterozygous LoFs: 191
Defined: 125748
p: 0.000768

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.648	449	412	1.09	0.0000253	4778
Missense (PolyPhen)		124	117.33	1.0569		1482
Synonymous	-0.0906	164	163	1.01	0.00000989	1444
Loss of Function	1.06	36	43.5	0.827	0.00000265	452

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00031	0.00031	rare
Latino/Admixed American	0.00032	0.00032	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.0011	0.0011	notable
Finnish	0.0018	0.0016	notable
European (Non-Finnish)	0.00077	0.00076	rare
South Asian	0.0010	0.0010	notable
Other	0.0010	0.00098	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Zinc endopeptidase with endothelin-3-converting enzyme activity. Cleaves EDN1, EDN2 and EDN3, with a marked preference for EDN3. {ECO:0000269|PubMed:10438732}.;

Recessive Scores

pRec: 0.218

Intolerance Scores

LoFtool: 0.234
RVIS EVS: -1.43
RVIS percentile EVS: 4

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.849

Gene Damage Prediction

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