KEL

Summary

KEL (Kell metallo-endopeptidase (Kell blood group), HGNC:6308) is a protein-coding gene on chromosome 7q34, encoding Kell blood group glycoprotein (P23276). Zinc endopeptidase with endothelin-3-converting enzyme activity.

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.

Source: NCBI Gene 3792 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 136 total — 2 pathogenic
• MANE Select transcript: NM_000420

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6308
Approved symbol	KEL
Name	Kell metallo-endopeptidase (Kell blood group)
Location	7q34
Locus type	gene with protein product
Status	Approved
Aliases	ECE3, CD238
Ensembl gene	ENSG00000197993
Ensembl biotype	protein_coding
OMIM	613883
Entrez	3792

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 4 protein_coding, 3 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000355265, ENST00000460479, ENST00000465697, ENST00000467543, ENST00000470850, ENST00000476829, ENST00000478969, ENST00000479768, ENST00000494148, ENST00000949853

RefSeq mRNA: 1 — MANE Select: NM_000420 NM_000420

CCDS: CCDS34766

Canonical transcript exons

ENST00000355265 — 19 exons

Exon	Start	End
ENSE00000728682	142942434	142942529
ENSE00000728685	142942875	142943044
ENSE00000728689	142943276	142943343
ENSE00000728710	142944643	142944741
ENSE00000728714	142946207	142946317
ENSE00001090607	142941114	142941413
ENSE00001815471	142962204	142962363
ENSE00003504359	142952509	142952638
ENSE00003506903	142957827	142957973
ENSE00003521382	142961795	142961872
ENSE00003585123	142961360	142961501
ENSE00003602880	142954184	142954372
ENSE00003610340	142943783	142943883
ENSE00003616565	142953808	142953956
ENSE00003625117	142960928	142961104
ENSE00003644818	142943486	142943596
ENSE00003674463	142944323	142944400
ENSE00003676692	142954465	142954527
ENSE00003789382	142958304	142958428

Expression profiles

Bgee: expression breadth ubiquitous, 131 present calls, max score 96.98.

FANTOM5 (CAGE): breadth broad, TPM avg 2.5135 / max 400.8247, expressed in 206 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
86651	2.4788	197
86649	0.0320	10
86650	0.0027	1

Top tissues by expression

134 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	96.98	gold quality
left testis	UBERON:0004533	96.61	gold quality
testis	UBERON:0000473	95.47	gold quality
bone marrow	UBERON:0002371	90.74	gold quality
bone marrow cell	CL:0002092	87.62	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	84.50	gold quality
lymph node	UBERON:0000029	83.37	gold quality
corpus callosum	UBERON:0002336	81.05	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.96	gold quality
blood	UBERON:0000178	79.83	gold quality
spleen	UBERON:0002106	78.02	gold quality
tonsil	UBERON:0002372	76.19	gold quality
substantia nigra	UBERON:0002038	76.06	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	74.81	gold quality
primary visual cortex	UBERON:0002436	72.31	gold quality
Ammon’s horn	UBERON:0001954	72.05	gold quality
putamen	UBERON:0001874	70.63	gold quality
temporal lobe	UBERON:0001871	69.46	gold quality
amygdala	UBERON:0001876	69.45	gold quality
ganglionic eminence	UBERON:0004023	68.74	gold quality
ventricular zone	UBERON:0003053	67.95	gold quality
lower esophagus mucosa	UBERON:0035834	67.49	gold quality
Brodmann (1909) area 9	UBERON:0013540	66.42	gold quality
endocervix	UBERON:0000458	66.21	gold quality
cerebral cortex	UBERON:0000956	65.97	gold quality
right frontal lobe	UBERON:0002810	65.95	gold quality
caudate nucleus	UBERON:0001873	65.92	gold quality
hypothalamus	UBERON:0001898	65.84	gold quality
placenta	UBERON:0001987	65.50	gold quality
monocyte	CL:0000576	65.45	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.83
E-MTAB-9067	yes	3.52

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SP1, SP3

miRNA regulators (miRDB)

9 targeting KEL, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-6737-3P	98.95	68.56	1577
HSA-MIR-7157-3P	98.95	68.70	1582
HSA-MIR-4764-5P	98.88	65.53	894
HSA-MIR-5008-3P	98.73	67.50	1433
HSA-MIR-5691	98.23	67.02	1335
HSA-MIR-6805-3P	98.23	67.02	1334
HSA-MIR-4642	97.52	67.60	916
HSA-MIR-6753-5P	94.70	64.08	470

Literature-anchored findings (GeneRIF, showing 28)

• x-ray analysis of Kell blood group protein (PMID:12842980)
• Kell K2 antigen is a catalytically active metalloprotease, but the rare Kell K1 antigen is inactive (PMID:15769748)
• KEL6 red blood cells have endothelin-3-converting enzyme activity (PMID:16423827)
• Results demonstrate the lack of Kell expression in rodent neuronal cells and strongly suggest the same for human cerebral tissue, in which the Kellprotein was exclusively observed on RBCs in cerebral blood vessels. (PMID:17379193)
• This is the first description of the KEL*1,3 allele encoding KEL1 and KEL3 on the same molecule. (PMID:19347978)
• In screening 87665 unrelated healthy blood donors in China, two K(0) probands were detected; in exon 3, 185insT (Ser62Phe and a premature stop codon in exon 4 (PMID:19747286)
• Novel IVS6-13C>T mutation recognized as a cause of discrepancy between phenotyping and genotyping in KEL*3,4 polymorphism identification. (PMID:20609202)
• Systematic DNA analysis showed that the number of discordant phenotype/genotype results, related to silent KEL*02 alleles was higher than expected in France. (PMID:23581578)
• These findings identify the translational start site and define the full cytoplasmic tail of the human Kell glycoprotein. (PMID:23721226)
• A compensatory mechanism of the KELmod allele deficient expression in heterozygote patients may exist. Retrospective analysis of 80,000 subjects showed a local KEL:1,-2 frequency 4 times lower than expected. (PMID:23727116)
• Sequence analysis of genomic DNA from 2 Caucasian Brazilian women revealed a new homozygous change in KEL Exon 2, a guanine to an adenine substitution at Position 71 (c.71G>A, NCBI_ss#: 831878329) leading to a premature stop codon. (PMID:24506314)
• A new allele, KEL(Thr193Met, Pro326Leu), has a drastic effect on the Kell glycoprotein probably due to defects in protein trafficking or reduced membrane integration. (PMID:24588083)
• A rare allele in this family has been numbered KEL*02M.04 and contains a Gly703Arg substitution that appears to cause weakened expression of Kell antigens and a Kmod phenotype when in trans with a null allele in the propositus. (PMID:24795954)
• High-throughput Kell, Kidd, and Duffy matrix-assisted laser desorption/ionization, time-of-flight mass spectrometry-based blood group genotyping of 4000 donors shows close to full concordance with serotyping and detects new alleles. (PMID:24845979)
• After sequencing the whole KEL gene, we found three new missense mutations: c.455A>G (p.Tyr152Cys) at Exon 5, c.2111A>C (p.Pro704His) at Exon 19, and c.1726G>C (p.Gly576Arg) at Exon 16. (PMID:25041236)
• A relatively increased KEL1 antigen expression in KEL:1,2null and KEL:1,2mod individuals suggest that the expression of Kell-XK complexes depends on the availability of the XK protein. (PMID:25156717)
• Through molecular genotyping we also identified polymorphisms in RhCE, Kell, Duffy, Colton, Lutheran and Scianna loci in donors and patients. (PMID:25582271)
• The expression of Kell glycoprotein on RBCs is not critical to the erythrocyte function (PMID:26308465)
• description of four new KEL*01M alleles (PMID:26996808)
• Ten new silent KEL alleles were identified in Japanese individuals with the Ko phenotype. (PMID:29280152)
• Leucoreduced red blood cells from transgenic mouse donors expressing high levels of the human KEL glycoprotein in an erythrocyte-specific manner (KEL(hi) donors) were transfused after the platelets, and anti-KEL responses were measured. Transfusion of platelets from wild-type C57BL/6 donors prior to KELhi red blood cell transfusion enhances the anti-KEL alloimmune response. (PMID:30418129)
• Identification of a novel null allele of the KEL gene in a Korean patient with the Kell null phenotype. (PMID:32598050)
• Diversity of variant alleles encoding Kidd, Duffy, and Kell antigens in individuals with sickle cell disease using whole genome sequencing data from the NHLBI TOPMed Program. (PMID:33231305)
• HLA-DRB1 molecules and the presentation of anchor peptides from RhD, RhCE, and KEL proteins. (PMID:33675036)
• Novel KEL*02N allele in Saudi Arabia encoding a Kell null (K0 ) phenotype. (PMID:34137046)
• Functional Evaluation of KEL as an Oncogenic Gene in the Progression of Acute Erythroleukemia. (PMID:35140839)
• Novel KEL allele associated with loss of Kp(b) identified in a white blood donor. (PMID:35852066)
• Epigenetic dissection of human blood group genes reveals regulatory elements and detailed characteristics of KEL and four other loci. (PMID:38644556)

Cross-species orthologs

37 orthologs

Organism	Symbol	Gene ID
mus_musculus	Kel	ENSMUSG00000029866
rattus_norvegicus	Kel	ENSRNOG00000015682
drosophila_melanogaster	goe	FBGN0027528
drosophila_melanogaster	Nepl21	FBGN0027578
drosophila_melanogaster	frma	FBGN0029769
drosophila_melanogaster	Nep1	FBGN0029843
drosophila_melanogaster	Nep6	FBGN0030425
drosophila_melanogaster	Nep3	FBGN0031081
drosophila_melanogaster	Nepl3	FBGN0031678
drosophila_melanogaster	Nepl5	FBGN0031808
drosophila_melanogaster	Nepl7	FBGN0032442
drosophila_melanogaster	Nepl8	FBGN0032585
drosophila_melanogaster	Nepl12	FBGN0037727
drosophila_melanogaster	Nep4	FBGN0038818
drosophila_melanogaster	Nepl13	FBGN0039022
drosophila_melanogaster	Nepl14	FBGN0039023
drosophila_melanogaster	Nepl15	FBGN0039024
drosophila_melanogaster	Nep7	FBGN0039564
drosophila_melanogaster	Nepl17	FBGN0039609
drosophila_melanogaster	Nepl18	FBGN0039611
drosophila_melanogaster	Nepl19	FBGN0039612
drosophila_melanogaster	Nepl20	FBGN0039613
drosophila_melanogaster	Nepl6	FBGN0259716
caenorhabditis_elegans		WBGENE00013785
caenorhabditis_elegans		WBGENE00013786
caenorhabditis_elegans		WBGENE00013926
caenorhabditis_elegans		WBGENE00016778
caenorhabditis_elegans		WBGENE00016896
caenorhabditis_elegans		WBGENE00017393
caenorhabditis_elegans		WBGENE00017550
caenorhabditis_elegans		WBGENE00017553
caenorhabditis_elegans		WBGENE00017554
caenorhabditis_elegans		WBGENE00017555
caenorhabditis_elegans		WBGENE00017557
caenorhabditis_elegans		WBGENE00018196
caenorhabditis_elegans		WBGENE00018227
caenorhabditis_elegans		WBGENE00020293

Paralogs (6): PHEX (ENSG00000102174), ECE1 (ENSG00000117298), MMEL1 (ENSG00000142606), ECE2 (ENSG00000145194), ECEL1 (ENSG00000171551), MME (ENSG00000196549)

Protein

Protein identifiers

Kell blood group glycoprotein — P23276 (reviewed: P23276)

All UniProt accessions (5): A0A077QP03, E7ETW3, E9PHG0, P23276, H0Y8A1

UniProt curated annotations — full annotation on UniProt →

Function. Zinc endopeptidase with endothelin-3-converting enzyme activity. Cleaves EDN1, EDN2 and EDN3, with a marked preference for EDN3.

Subunit / interactions. Heterodimer with XK; disulfide-linked.

Subcellular location. Cell membrane.

Tissue specificity. Expressed at high levels in erythrocytes and testis (in Sertoli cells), and, at lower levels, in skeletal muscle, tonsils (in follicular dendritic cells), lymph node, spleen and appendix (at protein level). Also expressed in many adult and fetal nonerythroid tissues, including brain, spleen, lymph nodes and bone marrow.

Post-translational modifications. N-glycosylated.

Cofactor. Binds 1 zinc ion per subunit.

Polymorphism. KEL is responsible for the Kell blood group system. The molecular basis of the K=KEL1/k=KEL2 blood group antigens is a single variation in position 193; Thr-193 corresponds to KEL2 and Met-193 to KEL1. The molecular basis of the Kpa=KEL3/Kpb=KEL4/Kpc=KEL21 blood group antigens is a single variation in position 281; Arg-281 corresponds to KEL4, Trp-281 to KEL3 and Gln-281 to KEL21. The molecular basis of the Jsa=KEL6/Jsb=KEL7 blood group antigens is a single variation in position 597; Leu-597 corresponds to KEL7 and Pro-597 to KEL6. The molecular basis of the KEL11/KEL17 blood group antigens is a single variation in position 302; Val-302 corresponds to KEL11 and Ala-302 to KEL17. The molecular basis of the KEL14/KEL24 blood group antigens is a single variation in position 180; Arg-180 corresponds to KEL14 and Pro-180 to KEL24.

Similarity. Belongs to the peptidase M13 family.

RefSeq proteins (1): NP_000411* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000718	Peptidase_M13	Family
IPR008753	Peptidase_M13_N	Domain
IPR018497	Peptidase_M13_C	Domain
IPR024079	MetalloPept_cat_dom_sf	Homologous_superfamily
IPR042089	Peptidase_M13_dom_2	Homologous_superfamily

Pfam: PF01431, PF05649

UniProt features (43 total): sequence variant 16, disulfide bond 6, glycosylation site 5, binding site 3, mutagenesis site 3, topological domain 2, region of interest 2, active site 2, chain 1, modified residue 1, transmembrane region 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P23276-F1	87.46	0.64

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (2): 582; 638 (proton donor)

Ligand- & substrate-binding residues (3): 585; 634; 581

Post-translational modifications (1): 7

Disulfide bonds (6): 72, 77–82, 100–717, 108–682, 155–410, 610–729

Glycosylation sites (5): 94, 115, 191, 345, 627

Mutagenesis-validated functional residues (3):

Position	Phenotype
72	loss of kell-xk complex.
319	no loss of kell-xk complex.
582	loss of catalytic activity.

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-375276	Peptide ligand-binding receptors
R-HSA-162582	Signal Transduction
R-HSA-372790	Signaling by GPCR
R-HSA-373076	Class A/1 (Rhodopsin-like receptors)
R-HSA-500792	GPCR ligand binding

MSigDB gene sets: 147 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GNF2_PRDX2, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOMF_METALLOPEPTIDASE_ACTIVITY, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, IVANOVA_HEMATOPOIESIS_MATURE_CELL, GOBP_NEUROGENESIS, GGGTGGRR_PAX4_03, GOBP_MONOATOMIC_CATION_TRANSPORT, GNF2_ANK1, GOBP_REGULATION_OF_ANATOMICAL_STRUCTURE_SIZE, REACTOME_PEPTIDE_LIGAND_BINDING_RECEPTORS, GOBP_PROTEIN_MATURATION

GO Biological Process (12): intracellular calcium ion homeostasis (GO:0006874), regulation of cell size (GO:0008361), intracellular magnesium ion homeostasis (GO:0010961), protein processing (GO:0016485), regulation of axon diameter (GO:0031133), vasoconstriction (GO:0042310), myelination (GO:0042552), skeletal muscle fiber development (GO:0048741), establishment of localization in cell (GO:0051649), potassium ion transmembrane transport (GO:0071805), negative regulation of potassium ion transmembrane transport (GO:1901380), proteolysis (GO:0006508)

GO Molecular Function (6): metalloendopeptidase activity (GO:0004222), metal ion binding (GO:0046872), protein binding (GO:0005515), peptidase activity (GO:0008233), metallopeptidase activity (GO:0008237), hydrolase activity (GO:0016787)

GO Cellular Component (5): nucleoplasm (GO:0005654), Golgi apparatus (GO:0005794), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-4 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
intracellular monoatomic cation homeostasis	2
cytoplasm	2
calcium ion homeostasis	1
regulation of cellular component size	1
magnesium ion homeostasis	1
proteolysis	1
protein maturation	1
regulation of cell projection size	1
regulation of axonogenesis	1
blood vessel diameter maintenance	1
axon ensheathment	1
skeletal muscle tissue development	1
myotube cell development	1
establishment of localization	1
cellular localization	1
potassium ion transport	1
monoatomic cation transmembrane transport	1
negative regulation of potassium ion transport	1
potassium ion transmembrane transport	1
regulation of potassium ion transmembrane transport	1
negative regulation of cation transmembrane transport	1
protein metabolic process	1
endopeptidase activity	1
metallopeptidase activity	1
cation binding	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
catalytic activity	1
nuclear lumen	1
endomembrane system	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

834 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KEL	XK	P51811	896
KEL	XKR3	Q5GH77	887
KEL	XKRX	Q6PP77	865
KEL	EDN3	P14138	814
KEL	PIP	P12273	775
KEL	VPS13A	Q96RL7	728
KEL	RHCE	P18577	722
KEL	H3BT10	H3BT10	650
KEL	GYPB	P06028	603
KEL	EDN2	P20800	560
KEL	FUT2	Q10981	555
KEL	BCAM	P50895	549
KEL	SLC14A1	Q13336	542
KEL	XKR4	Q5GH76	530
KEL	GYPA	P02724	520

IntAct

35 interactions, top by confidence:

A	B	Type	Score
KEL	PM20D2	psi-mi:“MI:0915”(physical association)	0.560
KEL	ADIPOQ	psi-mi:“MI:0915”(physical association)	0.560
C5	KEL	psi-mi:“MI:0915”(physical association)	0.560
KEL	CLDN19	psi-mi:“MI:0915”(physical association)	0.560
KEL	TTMP	psi-mi:“MI:0915”(physical association)	0.560
KEL	SERPINH1	psi-mi:“MI:0915”(physical association)	0.560
KEL	PRKACA	psi-mi:“MI:0915”(physical association)	0.560
KEL	TGFBR2	psi-mi:“MI:0915”(physical association)	0.560
SLC4A1	FLOT1	psi-mi:“MI:0914”(association)	0.530
AKT1	KEL	psi-mi:“MI:0915”(physical association)	0.450
AKT1	KEL	psi-mi:“MI:2364”(proximity)	0.450
KEL	TUBA1A	psi-mi:“MI:0915”(physical association)	0.370
EWSR1	KEL	psi-mi:“MI:0915”(physical association)	0.370
CUL3	PXDNL	psi-mi:“MI:0914”(association)	0.350
KEL	SELENOT	psi-mi:“MI:0914”(association)	0.350
KEL	SPOP	psi-mi:“MI:2364”(proximity)	0.270
SPOP	KEL	psi-mi:“MI:2364”(proximity)	0.270
KEL	PM20D2	psi-mi:“MI:0915”(physical association)	0.000
ADIPOQ	KEL	psi-mi:“MI:0915”(physical association)	0.000
CLDN19	KEL	psi-mi:“MI:0915”(physical association)	0.000
C5	KEL	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (13): KEL (Two-hybrid), KEL (Two-hybrid), KEL (Two-hybrid), KEL (Two-hybrid), KEL (Two-hybrid), KEL (Two-hybrid), SELT (Affinity Capture-MS), FLVCR1 (Affinity Capture-MS), SLC16A10 (Affinity Capture-MS), KEL (Cross-Linking-MS (XL-MS)), TUBA1A (Two-hybrid), KEL (Affinity Capture-MS), KEL (Reconstituted Complex)

ESM2 similar proteins: A0A1B0GTW7, A0A1D5NSK0, A0A1L8HYT7, A0A286YEC0, G7PWZ3, O77755, O88959, P0C0K7, P17490, P23276, P43021, P51882, P59509, P59996, P70505, Q02853, Q04912, Q04962, Q04997, Q0V8J4, Q0VAY3, Q17R55, Q3U435, Q499S5, Q4R7Z5, Q58Y75, Q62190, Q6MG64, Q76MJ5, Q7TN88, Q7Z442, Q80W65, Q8BMN4, Q8CJH3, Q8IVN8, Q8VCS0, Q91X21, Q96KR4, Q96PQ0, Q96S42

Diamond homologs: A0A0B4K692, B2RQR8, F1N476, O16796, O44857, O95672, P07861, P08049, P08473, P0C1T0, P0DPD6, P0DPD8, P0DPD9, P0DPE2, P23276, P42891, P42892, P42893, P70669, P78562, P97739, Q18673, Q22523, Q495T6, Q4PZA2, Q5RE69, Q61391, Q8IS64, Q8T062, Q9EQF2, Q9JHL3, Q9JLI3, Q9JMI0, Q9W436, Q9W5Y0, W4VS99, A5PK19, A5WVX1, P0DPD7, P0DPE0

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
KEL	“up-regulates activity”	EDN3	cleavage

Disease & clinical

Clinical variants and AI predictions

ClinVar

136 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	97
Likely benign	14
Benign	7

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
17723	NM_000420.3(KEL):c.223+1G>C	Pathogenic
2576608	NM_000420.3(KEL):c.400+1G>A	Pathogenic

SpliceAI

2960 predictions. Top by Δscore:

Variant	Effect	Δscore
7:142942525:TATGC:T	acceptor_gain	1.0000
7:142942526:ATGC:A	acceptor_gain	1.0000
7:142942527:TGC:T	acceptor_gain	1.0000
7:142942528:GC:G	acceptor_gain	1.0000
7:142942529:CC:C	acceptor_gain	1.0000
7:142942530:C:CC	acceptor_gain	1.0000
7:142942530:C:CG	acceptor_loss	1.0000
7:142942534:G:C	acceptor_gain	1.0000
7:142942534:G:GC	acceptor_gain	1.0000
7:142942540:G:C	acceptor_gain	1.0000
7:142942540:G:GC	acceptor_gain	1.0000
7:142942871:ATAC:A	donor_loss	1.0000
7:142942872:TA:T	donor_loss	1.0000
7:142943045:C:CC	acceptor_gain	1.0000
7:142943274:A:AC	donor_gain	1.0000
7:142943275:C:CC	donor_gain	1.0000
7:142943275:CAGAG:C	donor_gain	1.0000
7:142943279:G:C	donor_gain	1.0000
7:142943339:CGGCT:C	acceptor_gain	1.0000
7:142943342:CT:C	acceptor_gain	1.0000
7:142943344:C:CC	acceptor_gain	1.0000
7:142943480:CCATA:C	donor_loss	1.0000
7:142943481:CATAC:C	donor_loss	1.0000
7:142943482:ATAC:A	donor_loss	1.0000
7:142943483:TA:T	donor_loss	1.0000
7:142943485:C:A	donor_loss	1.0000
7:142943593:CCAC:C	acceptor_gain	1.0000
7:142943594:CACC:C	acceptor_gain	1.0000
7:142943595:ACC:A	acceptor_loss	1.0000
7:142943596:CCT:C	acceptor_loss	1.0000

AlphaMissense

4801 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:142953935:A:G	W316R	0.981
7:142953935:A:T	W316R	0.981
7:142942443:G:C	S676R	0.961
7:142942443:G:T	S676R	0.961
7:142942445:T:G	S676R	0.961
7:142957964:A:G	W179R	0.957
7:142957964:A:T	W179R	0.957
7:142941318:A:C	F711L	0.954
7:142941318:A:T	F711L	0.954
7:142941320:A:G	F711L	0.954
7:142953933:C:A	W316C	0.945
7:142953933:C:G	W316C	0.945
7:142952569:G:C	F381L	0.933
7:142952569:G:T	F381L	0.933
7:142952571:A:G	F381L	0.933
7:142941257:A:G	W732R	0.932
7:142941257:A:T	W732R	0.932
7:142954188:A:G	L307P	0.924
7:142954526:A:T	I225K	0.921
7:142943329:C:T	G573D	0.917
7:142946300:C:A	W407C	0.917
7:142946300:C:G	W407C	0.917
7:142943503:G:C	F562L	0.916
7:142943503:G:T	F562L	0.916
7:142943505:A:G	F562L	0.916
7:142946292:C:G	C410S	0.915
7:142946293:A:T	C410S	0.915
7:142943331:A:C	F572L	0.914
7:142943331:A:T	F572L	0.914
7:142943333:A:G	F572L	0.914

dbSNP variants (sampled 300 via entrez): RS1000450200 (7:142959706 C>G,T), RS1000519634 (7:142959371 T>C), RS1000746558 (7:142961944 C>G), RS1000763123 (7:142955130 G>A), RS1000789509 (7:142957053 C>T), RS1001151112 (7:142950798 C>T), RS1001436974 (7:142951145 C>T), RS1001459393 (7:142955568 G>A), RS1001654013 (7:142948804 C>T), RS1001722217 (7:142956424 T>A,C), RS1001737363 (7:142948470 G>T), RS1001814188 (7:142955812 C>A,T), RS1002023817 (7:142946860 C>A,T), RS1002233599 (7:142962668 T>C,G), RS1002348679 (7:142960092 C>T)

Disease associations

OMIM: gene MIM:613883 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): vein of Galen aneurysm (MONDO:0015196)

Orphanet (1): Vein of Galen malformation (Orphanet:1053)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST004611_29	High light scatter reticulocyte count	4.000000e-09
GCST004612_20	High light scatter reticulocyte percentage of red cells	7.000000e-09
GCST004628_96	Immature fraction of reticulocytes	2.000000e-15
GCST004860_10	Alcoholic chronic pancreatitis	3.000000e-06
GCST90002385_153	High light scatter reticulocyte count	8.000000e-17
GCST90002386_464	High light scatter reticulocyte percentage of red cells	2.000000e-17
GCST90002387_389	Immature fraction of reticulocytes	2.000000e-16
GCST90002387_390	Immature fraction of reticulocytes	2.000000e-15

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007986	reticulocyte count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C536535	Vein of Galen aneurysm (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	decreases expression	1
phosphoramidon	affects binding, affects metabolic processing	1
CGP 52608	affects binding, increases reaction	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Diethylhexyl Phthalate	decreases expression	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Methyl Methanesulfonate	increases expression	1
Okadaic Acid	decreases expression	1

Cellosaurus cell lines

5 cell lines: 3 transformed cell line, 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_AV04	Chor-IN-1	Cancer cell line	Male
CVCL_C0XE	BEL-A KEL KO	Transformed cell line	Sex unspecified
CVCL_C0XH	BEL-A 4x KO	Transformed cell line	Sex unspecified
CVCL_C0XI	BEL-A 5x KO	Transformed cell line	Sex unspecified
CVCL_E8PH	MEL.KEL.24	Cancer cell line

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.