HAVCR1

Summary

HAVCR1 (hepatitis A virus cellular receptor 1, HGNC:17866) is a protein-coding gene on chromosome 5q33.3, encoding Hepatitis A virus cellular receptor 1 (Q96D42). Phosphatidylserine receptor that plays an important functional role in regulatory B-cell homeostasis including generation, expansion and suppressor functions.

The protein encoded by this gene is a membrane receptor for both human hepatitis A virus (HHAV) and TIMD4. The encoded protein may be involved in the moderation of asthma and allergic diseases. The reference genome represents an allele that retains a MTTVP amino acid segment that confers protection against atopy in HHAV seropositive individuals. The protein is a receptor for multiple other viruses, including Ebola virus, Marburg virus, Dengue virus, and Zika virus and is a possible entry factor for SARS-CoV-2 and other coronaviruses.

Source: NCBI Gene 26762 — RefSeq curated summary.

At a glance

• GWAS associations: 25
• Clinical variants (ClinVar): 82 total
• MANE Select transcript: NM_001173393

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17866
Approved symbol	HAVCR1
Name	hepatitis A virus cellular receptor 1
Location	5q33.3
Locus type	gene with protein product
Status	Approved
Aliases	HAVCR-1, TIM-1, TIM1, HAVCR, TIMD1, CD365, KIM1
Ensembl gene	ENSG00000113249
Ensembl biotype	protein_coding
OMIM	606518
Entrez	26762

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

ENST00000339252, ENST00000522693, ENST00000523175, ENST00000698790, ENST00000699093, ENST00000953673, ENST00000953674

RefSeq mRNA: 3 — MANE Select: NM_001173393 NM_001173393, NM_001308156, NM_012206

CCDS: CCDS43392, CCDS78076

Canonical transcript exons

ENST00000523175 — 9 exons

Exon	Start	End
ENSE00000797217	157049038	157049145
ENSE00001023164	157052361	157052654
ENSE00001023167	157032854	157032887
ENSE00001133283	157055201	157055533
ENSE00002104290	157057898	157057955
ENSE00002111462	157058921	157059116
ENSE00002134289	157029413	157029841
ENSE00003598425	157037247	157037361
ENSE00003655645	157042627	157042682

Expression profiles

Bgee: expression breadth ubiquitous, 123 present calls, max score 78.88.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.7990 / max 174.1792, expressed in 112 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
64492	0.5153	97
64493	0.2487	62
64491	0.0182	7
203767	0.0169	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.88	gold quality
adult mammalian kidney	UBERON:0000082	72.93	gold quality
rectum	UBERON:0001052	71.96	gold quality
metanephros cortex	UBERON:0010533	71.81	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	71.64	gold quality
kidney	UBERON:0002113	71.35	gold quality
cortex of kidney	UBERON:0001225	71.27	gold quality
granulocyte	CL:0000094	69.87	gold quality
colonic epithelium	UBERON:0000397	69.31	gold quality
lymph node	UBERON:0000029	66.57	gold quality
blood	UBERON:0000178	62.93	gold quality
endometrium	UBERON:0001295	61.69	gold quality
islet of Langerhans	UBERON:0000006	60.12	gold quality
sural nerve	UBERON:0015488	58.35	silver quality
vermiform appendix	UBERON:0001154	58.25	gold quality
mucosa of transverse colon	UBERON:0004991	56.32	gold quality
transverse colon	UBERON:0001157	55.07	gold quality
gall bladder	UBERON:0002110	54.44	gold quality
bone marrow	UBERON:0002371	53.75	gold quality
leukocyte	CL:0000738	53.59	gold quality
apex of heart	UBERON:0002098	53.27	gold quality
right lung	UBERON:0002167	52.56	gold quality
monocyte	CL:0000576	52.17	gold quality
tonsil	UBERON:0002372	51.95	gold quality
spleen	UBERON:0002106	51.39	gold quality
colon	UBERON:0001155	51.03	gold quality
calcaneal tendon	UBERON:0003701	50.50	gold quality
upper lobe of left lung	UBERON:0008952	50.42	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	50.18	gold quality
hindlimb stylopod muscle	UBERON:0004252	49.98	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.49
E-GEOD-36552	no	248.03
E-CURD-11	no	60.58

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): PAX1, STAT3

miRNA regulators (miRDB)

25 targeting HAVCR1, 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-340-5P	100.00	72.50	4437
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-4255	99.72	67.70	1541
HSA-MIR-377-5P	99.70	65.28	712
HSA-MIR-6086	99.70	65.38	699
HSA-MIR-3171	99.49	69.06	776
HSA-MIR-142-5P	99.48	70.92	2416
HSA-MIR-5590-3P	99.48	70.91	2429
HSA-MIR-548AV-3P	99.43	68.50	1721
HSA-MIR-130A-5P	99.33	70.26	2623
HSA-MIR-4738-3P	98.98	67.98	1846
HSA-MIR-3130-5P	98.14	66.00	711
HSA-MIR-124-5P	98.11	67.65	1095
HSA-MIR-615-5P	98.10	63.76	591
HSA-MIR-4482-5P	97.53	65.68	598
HSA-MIR-6807-5P	97.51	64.25	1046
HSA-MIR-4759	97.39	65.86	608
HSA-MIR-383-5P	96.86	67.55	820
HSA-MIR-3117-3P	95.96	67.82	473
HSA-MIR-7704	95.30	62.35	115
HSA-MIR-4793-3P	94.87	65.85	896
HSA-MIR-6890-5P	92.89	65.83	442
HSA-MIR-585-3P	91.80	66.07	57

Literature-anchored findings (GeneRIF, showing 40)

• asthma susceptibility gene (PMID:11725301)
• shedding of KIM-1 in the regenerating kidney constitutes an active mechanism allowing dedifferentiated regenerating cells to scatter on basement membrane and reconstitute a continuous epithelial layer (PMID:12138159)
• Polymorphisms in hHAVcr-1 are not associated with atopic asthma in the Japanese population. (PMID:12618867)
• protective effects of hepatitis A virus on atopic disease depends on a common TIM-1 allele (PMID:14534576)
• The exon 4 variation site in human Tim-1 gene is associated with the susceptibility to allergic disease (PMID:14630400)
• Our results strongly suggest that the 5383_5397del variation site of Tim-1 exon 4 might be associated with atopic dermatitis susceptibility. (PMID:14637143)
• Review discusses recent studies demonstrating that the TIM family, particularly TIM-1, plays a critical role in immune responses that regulate the development of atopic diseases. (PMID:15007635)
• is expressed at higher levels in clear cell renal cell carcinoma (PMID:15086915)
• The two polymorphism sites of TIM-1 are not associated with allergic asthma in Chinese children. (PMID:15300647)
• co-immobilized recombinant eTim-1 was able to inhibit T cell activation mediated by CD3 + CD28 mAb (PMID:16481347)
• Kim1 is a novel regulatory molecule of flow-induced calcium signaling in kidney cells (PMID:17205356)
• IgA1lambda is a specific ligand of HAVCR1/TIM1 and that their association has a synergistic effect in virus-receptor interactions (PMID:17229699)
• TIM-1 is a critical component of the human T cell response and provide a mechanistic hypothesis for the role of TIM-1 in disease. (PMID:17371991)
• A variation site in the TIM-1 promoter region is associated with asthma susceptibility in a Chinese Han population. (PMID:17570927)
• Involved in the pathogenesis of systemic lupus erythematosus. (PMID:18052965)
• TIM-4 and TIM-1 are immunologically restricted members of the group of receptors whose recognition of PS is critical for the efficient clearance of apoptotic cells and prevention of autoimmunity. (PMID:18082433)
• Urinary excretion of KIM-1 is an independent predictor of long-term graft loss after kidney transplantation. (PMID:18165774)
• identify Kim1 as an endogenous ciliary protein (PMID:18273441)
• The present results suggest that the higher TIM1 expression associated with the protective TIM1 promoter haplotype confers protection against cerebral malaria. (PMID:18294362)
• a pathway from Tim-1 tyrosine phosphorylation to the PI3K signaling pathway appears to be a major effector of Tim-1-mediated T cell activation (PMID:18453570)
• Upregulation of kidney injury molecule-1 (KIM-1), a specific injury marker, is demonstrated in proximal tubular cells in urate nephropathy. (PMID:18715847)
• KIM-1 has a role in the clearance of debris from damaged renal tubules in acute kidney injury. (PMID:18769021)
• For humans, carriers of particular Tim-1 alleles, infection with hepatitis A virus (binds to Tim-1)protects from atopy (PMID:18802347)
• negative association between Hepatitis A virus seropositivity and atopic disease (PMID:19167431)
• KIM-1 can be used as human urinary renal dysfunction biomarker. (PMID:19173034)
• Dipsticks can provide a sensitive and accurate detection of HAVCR1. (PMID:19387469)
• Blocking the TIM-1 pathway is now emerging as a successful strategy to promote experimental peripheral transplantation tolerance. (PMID:19424017)
• gene polymorphism is associated with elevated serum total IgE levels, particularly in individuals with atopic asthma in middle China (PMID:19476019)
• First data on the expression of TIM-1 molecules in sarcoidosis. (PMID:19480659)
• haplotypes including TIM-1 genetic variants confer susceptibility to asthma in a Chinese population (PMID:19494522)
• Kim-1 is a promising novel marker for the early, organ specific and noninvasive detection of brain death-induced donor kidney damage. (PMID:19522876)
• KIM-1 performed best as an early biomarker for acute kidney injury (PMID:19572801)
• TIM-1 gene polymorphisms (-416G>C and -1454G>A) are associated with allergic rhinitis susceptibility in a Han Chinese population. (PMID:20232767)
• urinary KIM-1 is a associated acute kidney injury (PMID:20233133)
• KIM-1 mRNA may be useful biomarker of tubular damage associated with calcineurin inhibitor nephrotoxicity nd tubular atrophy in kidney transplantation. (PMID:20304168)
• KIM-1 is a specific biomarker for injuried kidney proximal tubules and the corresponding neoplasms, and has a high specificity and sensitivity for primary or metastatic clear cell renal cell carcinomas. (PMID:20388397)
• KIM-1 is expected to be a therapeutic target for kidney injury (PMID:20447817)
• TIM1 D3-A haplotype is associated with the delay of disease progression to AIDS in the HIV-1 infected Thai females. (PMID:20479636)
• Significant upregulation of LCN2 and HAVCR1 could be detected in the delayed kidney graft funtion group. Prognostic value of the two biomarkers together with donor age ranges between 75% and 83%. (PMID:20819195)
• lower urinary KIM-1 and NAG levels were associated with the regression of microalbuminuria in type 1 diabetes mellitus (PMID:20980978)

Cross-species orthologs

17 orthologs

Organism	Symbol	Gene ID
mus_musculus	Havcr1	ENSMUSG00000040405
mus_musculus	Timd2	ENSMUSG00000040413
mus_musculus	Timd6	ENSMUSG00000046974
mus_musculus	Timd5	ENSMUSG00000078924
rattus_norvegicus	Havcr1	ENSRNOG00000007243
rattus_norvegicus	Timd2	ENSRNOG00000021345
rattus_norvegicus	Havcr1l2	ENSRNOG00000042265
rattus_norvegicus	Havcr1l1	ENSRNOG00000043422
caenorhabditis_elegans		WBGENE00018289
caenorhabditis_elegans		WBGENE00020483
caenorhabditis_elegans		WBGENE00020484
caenorhabditis_elegans		WBGENE00020487
caenorhabditis_elegans		WBGENE00020785
caenorhabditis_elegans		WBGENE00021162
caenorhabditis_elegans		WBGENE00077592
caenorhabditis_elegans		WBGENE00195168
caenorhabditis_elegans		WBGENE00206360

Paralogs (3): HAVCR2 (ENSG00000135077), TIMD4 (ENSG00000145850), MED7 (ENSG00000155868)

Protein

Protein identifiers

Hepatitis A virus cellular receptor 1 — Q96D42 (reviewed: Q96D42)

Alternative names: Kidney injury molecule 1, T-cell immunoglobulin and mucin domain-containing protein 1, T-cell immunoglobulin mucin receptor 1, T-cell membrane protein 1

All UniProt accessions (4): Q96D42, A0A8V8TMP5, A0A8V8TPG0, E9PFX0

UniProt curated annotations — full annotation on UniProt →

Function. Phosphatidylserine receptor that plays an important functional role in regulatory B-cell homeostasis including generation, expansion and suppressor functions. As P-selectin/SELPLG ligand, plays a specialized role in activated but not naive T-cell trafficking during inflammatory responses. Controls thereby T-cell accumulation in the inflamed central nervous system (CNS) and the induction of autoimmune disease. Also regulates expression of various anti-inflammatory cytokines and co-inhibitory ligands including IL10. Acts as a regulator of T-cell proliferation. Confers phagocytic ability on injured kidney epithelial cells, allowing them to bind to and internalize apoptotic bodies and necrotic debris following kidney injury. The ectodomain binds to the surface of apoptotic kidney epithelial cells via phosphatidylserine and oxidized phospholipids exposed on the cell membrane of the apoptotic cells. HAVCR1-expressing cells are also capable of phagocytosing Gram-negative and Gram-positive bacteria. (Microbial infection) Acts as a receptor for Hepatitis A virus. (Microbial infection) Acts as a receptor for Ebolavirus and Marburg virus by binding exposed phosphatidyl-serine at the surface of virion membrane. Serves as a dual receptor for Ebolavirus by also interacting with envelope glycoprotein GP. (Microbial infection) Acts as a receptor for Dengue virus by binding exposed phosphatidyl-serine at the surface of virion membrane. TIM1 and Dengue virus are co-internalized during virus entry. (Microbial infection) Acts as a receptor for Zika virus by binding to envelope protein E. (Microbial infection) Plays a positive role in Chikungunya virus cell entry.

Subunit / interactions. Interacts with STAM. Interacts with SELPLG. Interacts with CD5L; interaction of HAVCR1 expressed on the surface of injured kidney tubular epithelial cells with CD5L promotes HAVCR1-mediated phagocytosis of intraluminal necrotic debris and contributes to kidney tissue repair. (Microbial infection) Interacts with hepatitis A virus capsid proteins. (Microbial infection) Interacts with Ebolavirus envelope glycoprotein GP. (Microbial infection) Interacts with Zika virus envelope protein E.

Subcellular location. Cell membrane. Cell projection. Phagocytic cup. Cytoplasmic vesicle. Phagosome.

Tissue specificity. Widely expressed, with highest levels in kidney and testis. Expressed by activated CD4+ T-cells during the development of helper T-cells responses.

Post-translational modifications. Ubiquitinated at two lysine residues Lys-338 and Lys-346 on its cytoplasmic domain. Ubiquitination promotes receptor endocytosis and target receptors for lysosomal degradation and termination of receptor signaling. (Microbial infection) Ubiquitination is required for Dengue virus endocytosis.

Induction. Up-regulated in the kidney in renal diseases (at protein level).

Polymorphism. The region containing tandem repeats is polymorphic and the sequence shown here corresponds to the most common allele. An association between hepatitis A virus (HAV) infection and atopic diseases has been observed in individuals with that allele. Allelic variation does not affect HAV-infection rates in Caucasians, Asians and African Americans.

Miscellaneous. The extracellular part of the protein can be cleaved and detected in urine and is in correlation with the expression in the kidney.

Similarity. Belongs to the immunoglobulin superfamily. TIM family.

RefSeq proteins (3): NP_001166864, NP_001295085, NP_036338 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003006	Ig/MHC_CS	Conserved_site
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013106	Ig_V-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR052331	TIM_domain-containing_protein	Family

Pfam: PF07686

UniProt features (52 total): repeat 12, strand 9, mutagenesis site 6, glycosylation site 4, disulfide bond 3, sequence variant 3, region of interest 2, topological domain 2, cross-link 2, helix 2, signal peptide 1, chain 1, compositionally biased region 1, transmembrane region 1, sequence conflict 1, turn 1, domain 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
5DZO	X-RAY DIFFRACTION	1.3
5F70	X-RAY DIFFRACTION	1.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96D42-F1	65.95	0.23

Functional residue map

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

Post-translational modifications (2): 338, 346

Disulfide bonds (3): 36–105, 46–57, 52–104

Glycosylation sites (4): 65, 263, 277, 291

Mutagenesis-validated functional residues (6):

Position	Phenotype
114	about 60% loss of chikungunya virus entry.
115	about 25% loss of chikungunya virus entry.
338	about 50% loss of ubiquitination.
338	complete loss of ubiquitination; when associated with r-346.
346	about 50% loss of ubiquitination.
346	complete loss of ubiquitination; when associated with r-338.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-9694614	Attachment and Entry
R-HSA-9918485	Dengue Virus Attachment and Entry

MSigDB gene sets: 118 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOCC_CELL_SURFACE, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_MAST_CELL_ACTIVATION, GOBP_MYELOID_LEUKOCYTE_ACTIVATION, GOBP_REGULATION_OF_MAST_CELL_ACTIVATION, GOBP_POSITIVE_REGULATION_OF_CELL_ACTIVATION, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_DN, GOBP_BIOLOGICAL_PROCESS_INVOLVED_IN_INTERACTION_WITH_HOST, GOBP_POSITIVE_REGULATION_OF_MAST_CELL_ACTIVATION, GOBP_VIRAL_LIFE_CYCLE, HNF1_C, GOBP_MEMBRANE_ORGANIZATION, GOBP_MEMBRANE_INVAGINATION

GO Biological Process (3): phagocytosis, engulfment (GO:0006911), positive regulation of mast cell activation (GO:0033005), symbiont entry into host cell (GO:0046718)

GO Molecular Function (3): virus receptor activity (GO:0001618), phosphatidylserine binding (GO:0001786), protein binding (GO:0005515)

GO Cellular Component (4): plasma membrane (GO:0005886), cell surface (GO:0009986), motile cilium (GO:0031514), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Early SARS-CoV-2 Infection Events	1
Dengue Virus Infection	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
phagocytosis	1
plasma membrane invagination	1
positive regulation of leukocyte activation	1
regulation of mast cell activation	1
mast cell activation	1
viral life cycle	1
symbiont entry into host	1
symbiont entry into host cell	1
exogenous protein binding	1
phospholipid binding	1
anion binding	1
modified amino acid binding	1
binding	1
membrane	1
cell periphery	1
cilium	1

Protein interactions and networks

STRING

1466 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HAVCR1	LCN2	P30150	913
HAVCR1	CST3	P01034	883
HAVCR1	FABP1	P07148	872
HAVCR1	TIMD4	Q96H15	846
HAVCR1	OGA	O60502	773
HAVCR1	IL18	Q14116	767
HAVCR1	SPP1	P10451	741
HAVCR1	IGFBP7	Q16270	720
HAVCR1	TFF3	Q07654	717
HAVCR1	ALB	P02768	716
HAVCR1	TNF	P01375	693
HAVCR1	CASP3	P42574	691
HAVCR1	CLU	P10909	665
HAVCR1	TIMP2	P16035	645
HAVCR1	B2M	P01884	645

IntAct

25 interactions, top by confidence:

A	B	Type	Score
HAVCR1	S	psi-mi:“MI:0407”(direct interaction)	0.670
HAVCR1	S	psi-mi:“MI:0915”(physical association)	0.670
S	HAVCR1	psi-mi:“MI:0915”(physical association)	0.670
	HAVCR1	psi-mi:“MI:0915”(physical association)	0.560
HAVCR1	IGHA1	psi-mi:“MI:0914”(association)	0.530
CD300LF	HAVCR1	psi-mi:“MI:0915”(physical association)	0.400
HAVCR1	HAVCR1	psi-mi:“MI:0915”(physical association)	0.400
HAVCR1	SIGLEC1	psi-mi:“MI:0915”(physical association)	0.400
HAVCR1	TIMD4	psi-mi:“MI:0915”(physical association)	0.400
HAVCR1	TYRO3	psi-mi:“MI:0915”(physical association)	0.400
HAVCR1	SLAMF6	psi-mi:“MI:0915”(physical association)	0.400
HAVCR1	TNFRSF10C	psi-mi:“MI:0915”(physical association)	0.400
TYRO3	HAVCR1	psi-mi:“MI:0915”(physical association)	0.400
BTN3A3	HAVCR1	psi-mi:“MI:0915”(physical association)	0.400
E	RAB34	psi-mi:“MI:0914”(association)	0.350
HAVCR1	UBQLN4	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (37): TNFRSF10B (Affinity Capture-MS), ACVR1B (Affinity Capture-MS), DDR2 (Affinity Capture-MS), TGFBR1 (Affinity Capture-MS), NDFIP1 (Affinity Capture-MS), STUB1 (Affinity Capture-MS), ABCG2 (Affinity Capture-MS), SNX17 (Affinity Capture-MS), PI4K2A (Affinity Capture-MS), UBA52 (Affinity Capture-MS), ATP1A1 (Affinity Capture-MS), SLC12A3 (Affinity Capture-MS), SNX6 (Affinity Capture-MS), ATP1B1 (Affinity Capture-MS), ITCH (Affinity Capture-MS)

ESM2 similar proteins: A4H220, A4H221, A4H222, A4H223, A4H238, A4H239, A4H240, A4H241, A4H243, A4H244, A4H245, A4H257, A4H258, A4H259, A4H260, O54947, P59647, P97808, Q17R60, Q30KK0, Q30KK1, Q30KK2, Q30KK3, Q30KK9, Q30KL1, Q30KQ4, Q32ZH2, Q3MIW9, Q5FVR0, Q5XI99, Q62170, Q64294, Q6MG22, Q6U7R4, Q7TST5, Q7Z7G0, Q8JZQ0, Q8N687, Q8R183, Q95152

Diamond homologs: O46598, O54947, P0C0K5, Q5FVR0, Q5QNS5, Q6U7R4, Q8R183, Q8TDQ0, Q8VIM0, Q96D42, Q96H15, Q3V3F6, Q6UWV2, O15389, Q08ET2, Q6ZMC9, A4QPC6, P78310, P97792, Q5R764, Q9R066

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	47
Likely benign	13
Benign	16

Top pathogenic / likely-pathogenic (0)

SpliceAI

1839 predictions. Top by Δscore:

Variant	Effect	Δscore
5:157029840:CA:C	acceptor_gain	1.0000
5:157037245:A:AC	donor_gain	1.0000
5:157037246:C:CT	donor_gain	1.0000
5:157037372:A:T	acceptor_gain	1.0000
5:157048051:G:C	acceptor_gain	1.0000
5:157048051:G:GC	acceptor_gain	1.0000
5:157049143:CTA:C	acceptor_gain	1.0000
5:157052425:TGGAA:T	donor_gain	1.0000
5:157052650:CTTGG:C	acceptor_gain	1.0000
5:157052652:TGG:T	acceptor_gain	1.0000
5:157052655:C:CC	acceptor_gain	1.0000
5:157052662:C:CT	acceptor_gain	1.0000
5:157052663:A:T	acceptor_gain	1.0000
5:157055194:AACTT:A	donor_loss	1.0000
5:157055195:ACTT:A	donor_loss	1.0000
5:157055196:CTT:C	donor_loss	1.0000
5:157055197:TTAC:T	donor_loss	1.0000
5:157055198:TA:T	donor_loss	1.0000
5:157055199:A:AC	donor_gain	1.0000
5:157055200:C:CG	donor_gain	1.0000
5:157055200:CG:C	donor_gain	1.0000
5:157055200:CGTG:C	donor_gain	1.0000
5:157055200:CGTGG:C	donor_gain	1.0000
5:157057894:TTA:T	donor_loss	1.0000
5:157057895:TACCT:T	donor_loss	1.0000
5:157057897:C:A	donor_loss	1.0000
5:157029842:C:CC	acceptor_gain	0.9900
5:157035669:A:AC	donor_gain	0.9900
5:157035786:T:TC	acceptor_gain	0.9900
5:157037240:GACTT:G	donor_loss	0.9900

AlphaMissense

2333 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:157055439:C:A	W47C	0.999
5:157055439:C:G	W47C	0.999
5:157055311:A:G	L90S	0.997
5:157055266:C:G	C105S	0.996
5:157055267:A:T	C105S	0.996
5:157055263:C:G	R106P	0.995
5:157055441:A:G	W47R	0.995
5:157055441:A:T	W47R	0.995
5:157055473:C:G	C36S	0.993
5:157055474:A:T	C36S	0.993
5:157055266:C:T	C105Y	0.992
5:157055272:T:C	Y103C	0.991
5:157055443:C:G	C46S	0.991
5:157055444:A:T	C46S	0.991
5:157055265:G:C	C105W	0.990
5:157055267:A:G	C105R	0.989
5:157055311:A:C	L90W	0.989
5:157055440:C:G	W47S	0.989
5:157055260:A:T	V107D	0.987
5:157055284:T:A	D99V	0.986
5:157055473:C:T	C36Y	0.986
5:157055273:A:C	Y103D	0.985
5:157055410:C:G	C57S	0.985
5:157055411:A:T	C57S	0.985
5:157055241:G:C	F113L	0.984
5:157055241:G:T	F113L	0.984
5:157055243:A:G	F113L	0.984
5:157055269:C:G	C104S	0.984
5:157055270:A:G	C104R	0.984
5:157055270:A:T	C104S	0.984

dbSNP variants (sampled 300 via entrez): RS1000034514 (5:157036434 G>A,C), RS1000052924 (5:157049120 C>T), RS1000104900 (5:157048784 C>A,T), RS1000106982 (5:157051970 A>G), RS1000191556 (5:157030632 T>G), RS1000214066 (5:157067926 C>T), RS1000243886 (5:157030837 C>T), RS1000246703 (5:157058055 G>A), RS1000397373 (5:157043163 T>A), RS1000407946 (5:157059764 A>G), RS1000494012 (5:157036817 A>G), RS1000636731 (5:157033770 A>C), RS1000796106 (5:157039739 G>T), RS1000817902 (5:157069280 C>T), RS1000884512 (5:157040900 C>T)

Disease associations

OMIM: gene MIM:606518 | disease phenotypes: MIM:613011, MIM:147050

GenCC curated gene-disease

Mondo (2): lymphoproliferative syndrome 1 (MONDO:0013081), IgE responsiveness, atopic (MONDO:0007817)

Orphanet (2): Combined immunodeficiency due to CD27 deficiency (Orphanet:238505), Combined immunodeficiency due to ITK deficiency (Orphanet:538963)

HPO phenotypes

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

GWAS associations

25 associations (top):

Study	Trait	p-value
GCST000287_11	LDL cholesterol	1.000000e-11
GCST000758_18	Triglycerides	4.000000e-12
GCST000759_14	LDL cholesterol	2.000000e-22
GCST000760_10	Cholesterol, total	7.000000e-28
GCST001905_8	Hypertriglyceridemia	3.000000e-06
GCST002896_15	Cholesterol, total	2.000000e-21
GCST002897_25	Triglycerides	2.000000e-11
GCST002898_14	LDL cholesterol	2.000000e-15
GCST006034_34	Total cholesterol levels	3.000000e-16
GCST006585_1668	Blood protein levels	2.000000e-60
GCST008074_87	Triglyceride levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	3.000000e-06
GCST008078_134	LDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	2.000000e-193
GCST008078_97	LDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	5.000000e-226
GCST008079_162	LDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	7.000000e-13
GCST008079_54	LDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	2.000000e-11
GCST008083_100	Triglyceride levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	2.000000e-06
GCST008990_1	Low density lipoprotein cholesterol levels	9.000000e-10
GCST009731_46	Blood protein levels in cardiovascular risk	2.000000e-145
GCST010173_45	Triglyceride levels	1.000000e-38
GCST010204_10	Low density lipoprotein cholesterol levels	2.000000e-69
GCST010500_4	T-Cell Immunoglobulin and Mucin domain 1 levels	8.000000e-120
GCST011345_4	Triglyceride levels	6.000000e-14
GCST011346_20	Total cholesterol levels	3.000000e-23
GCST011347_22	Low density lipoprotein cholesterol levels	1.000000e-13
GCST90002388_330	Lymphocyte count	1.000000e-10

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004530	triglyceride measurement
EFO:0004574	total cholesterol measurement
EFO:0004329	alcohol drinking
EFO:0010812	T-cell immunoglobulin and mucin domain 1 measurement
EFO:0004587	lymphocyte count

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C564133	Ige Responsiveness, Atopic (supp.)
C567815	Lymphoproliferative Syndrome, Ebv-Associated, Autosomal, 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

85 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases response to substance, increases reaction, decreases expression, increases expression	2
ochratoxin A	affects reaction, increases expression, decreases expression	2
Air Pollutants	affects expression, increases abundance, increases expression, affects cotreatment, decreases reaction	2
Benzo(a)pyrene	affects methylation, increases expression	2
Cisplatin	increases expression	2
Lipopolysaccharides	increases expression, affects response to substance	2
Aflatoxin B1	increases methylation, increases expression	2
fluxapyroxad	decreases expression	1
GSK-J4	increases expression	1
OTX015	decreases expression	1
mivebresib	decreases expression	1
allyl alcohol	increases expression	1
chlortoluron	decreases expression	1
di-n-octyl phthalate	increases abundance, increases secretion	1
ascorbate-2-phosphate	affects binding, affects cotreatment, increases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
perfluorooctanoic acid	increases expression	1
3-methyladenine	decreases reaction, increases expression	1
4-(2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acid	affects cotreatment, increases expression	1
S-(1,2-dichlorovinyl)cysteine	increases expression, affects response to substance	1
brequinar	decreases expression	1
chromium hexavalent ion	increases expression	1
esculentoside A	decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
liquiritigenin	decreases reaction, increases expression	1
CGP 52608	affects binding, increases reaction	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00414141	PHASE3	COMPLETED	Efficacy and Safety/Tolerability of Grass MATA MPL
NCT00423787	PHASE3	COMPLETED	Efficacy and Safety/Tolerability of Ragweed MATA MPL
NCT00104377	PHASE2	COMPLETED	Induction of Immunogenicity With Different Doses of Grass MATA in Subjects Allergic to Grass and Rye Pollen
NCT00110786	PHASE2	COMPLETED	Investigation of Efficacy and Safety of Ragweed MATAMPL, Pollinex-R and Placebo in Patients With Ragweed Allergy
NCT00113750	PHASE2	COMPLETED	Induction of Immunogenicity With Different Doses of TreeMATA in Subjects Allergic to Tree Pollen
NCT00118612	PHASE2	COMPLETED	Different Doses of Tyrosine Adsorbed Tree Pollen Allergoid With Monophosphoryl Lipid A (MPL) in Patients Sensitized to Tree Pollen
NCT00118625	PHASE2	COMPLETED	Assessment of the Contribution of Monophosphoryl Lipid A (MPL) to a Tree Pollen Allergy Vaccine
NCT00133146	PHASE2	COMPLETED	Assessment of the Contribution of Monophosphoryl Lipid A (MPL) to a Grass Pollen Allergy Vaccine
NCT00133159	PHASE2	COMPLETED	Different Doses of Tyrosine Adsorbed Grass Pollen Allergoid With Monophosphoryl Lipid A (MPL) in Patients Sensitized to Grass Pollen
NCT00258635	PHASE2	COMPLETED	Investigation of Safety+Efficacy of Different Doses of RagweedMATAMPL;Assessment of Residual Allergenicity Using Skin Prick Test
NCT00325338	PHASE2	COMPLETED	Follow-up Investigation of Efficacy of Ragweed MATAMPL,and Placebo in Patients With Ragweed-induced Seasonal Allergic Rhinitis
NCT00387478	PHASE2	TERMINATED	Investigation of Efficacy and Safety of Tree MATAMPL,Tree MATA, and Placebo in Patients With Birch-Induced Seasonal Allergic Rhinitis
NCT00461097	PHASE2	COMPLETED	Oral Immunotherapy for Childhood Egg Allergy
NCT00104390	PHASE1	COMPLETED	Assessment of Residual Allergenicity of Grass/Rye Pollen Allergoid Using Skin Prick Testing
NCT00107705	PHASE1	COMPLETED	Assessment of Residual Allergenicity of Tree (Birch, Hazel, and Alder) Pollen Allergoid Using Skin Prick Testing
NCT00109759	PHASE1	WITHDRAWN	Evaluation of Safety and Tolerability of Tyrosine Adsorbed Ragweed Pollen Allergoid With MPL (Monophosphoryl Lipid A)
NCT00116285	PHASE1	COMPLETED	Assessment of Residual Allergenicity of Ragweed Pollen Allergoid With Monophosphoryl Lipid A (MPL) Using Skin Prick Testing
NCT00241410	PHASE1	COMPLETED	Safety, Immunological Effect and Efficacy of the Combined Application of MPL and Grass Pollen Allergen
NCT00850668	PHASE1	COMPLETED	Peanut Allergy Vaccine Study in Healthy and Peanut-allergic Adults
NCT00580606	PHASE1/PHASE2	COMPLETED	A Randomized, Double-Blind Placebo-Controlled Peanut Sublingual Immunotherapy Trial
NCT01084174	PHASE1/PHASE2	COMPLETED	A Randomized, Double-Blind, Placebo-Controlled Pilot Study of Sublingual/Oral Immunotherapy for the Treatment of Peanut Allergy
NCT05003804	PHASE1/PHASE2	COMPLETED	Allergic Disease Onset Prevention Study
NCT01407640	Not specified	COMPLETED	Diagnosis and Physiopathology of Insulin Allergy
NCT02561390	Not specified	COMPLETED	Comparison Between spIgE and Skin Prick Test of Local and Imported Aeroallergens
NCT02561429	Not specified	COMPLETED	Comparison of Difference Histamine Concentration (1, 5 and 10 mg/ml) for Skin Prick Test Positive Control
NCT02733926	Not specified	UNKNOWN	Effect of Vegetation in Kindergartens on the Immune Response of Children
NCT06065137	Not specified	COMPLETED	Standardised Drug Provocation Testing in Perioperative Hypersensitivity