HHLA1

Summary

HHLA1 (HHLA1 neighbor of OC90, HGNC:4904) is a protein-coding gene on chromosome 8q24.22, encoding HERV-H LTR-associating protein 1 (C9JL84).

Predicted to be located in extracellular region.

Source: NCBI Gene 10086 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 101 total
• MANE Select transcript: NM_001145095

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4904
Approved symbol	HHLA1
Name	HHLA1 neighbor of OC90
Location	8q24.22
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000132297
Ensembl biotype	protein_coding
OMIM	604109
Entrez	10086

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 retained_intron

ENST00000414222, ENST00000473291, ENST00000673615

RefSeq mRNA: 1 — MANE Select: NM_001145095 NM_001145095

Canonical transcript exons

ENST00000414222 — 17 exons

Exon	Start	End
ENSE00001593453	132079718	132079966
ENSE00001597100	132095519	132095602
ENSE00001601985	132104108	132104167
ENSE00001648764	132095703	132095786
ENSE00001652697	132098882	132098962
ENSE00001656656	132089516	132089599
ENSE00001679687	132087845	132087901
ENSE00001694396	132061480	132064038
ENSE00001729799	132087653	132087739
ENSE00001770406	132100075	132100134
ENSE00001793722	132105187	132105286
ENSE00003465614	132076055	132076129
ENSE00003476891	132071340	132071493
ENSE00003489678	132077726	132077971
ENSE00003498461	132076475	132076543
ENSE00003608799	132065886	132065968
ENSE00003938375	132111102	132111157

Expression profiles

Bgee: expression breadth broad, 24 present calls, max score 76.70.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
type B pancreatic cell	CL:0000169	76.70	gold quality
olfactory bulb	UBERON:0002264	76.57	gold quality
diaphragm	UBERON:0001103	76.43	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	76.41	gold quality
secondary oocyte	CL:0000655	72.75	gold quality
vastus lateralis	UBERON:0001379	71.95	gold quality
quadriceps femoris	UBERON:0001377	71.06	gold quality
biceps brachii	UBERON:0001507	69.34	gold quality
myocardium	UBERON:0002349	69.16	gold quality
oocyte	CL:0000023	67.07	silver quality
cardiac muscle of right atrium	UBERON:0003379	66.98	gold quality
left ventricle myocardium	UBERON:0006566	66.71	gold quality
mucosa of paranasal sinus	UBERON:0005030	66.49	gold quality
decidua	UBERON:0002450	66.09	gold quality
parotid gland	UBERON:0001831	65.87	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	65.74	gold quality
epithelial cell of pancreas	CL:0000083	65.73	gold quality
hair follicle	UBERON:0002073	64.70	gold quality
heart right ventricle	UBERON:0002080	64.22	gold quality
nasal cavity epithelium	UBERON:0005384	63.96	gold quality
epithelium of nasopharynx	UBERON:0001951	63.94	gold quality
pancreatic ductal cell	CL:0002079	63.56	silver quality
tibia	UBERON:0000979	62.30	gold quality
choroid plexus epithelium	UBERON:0003911	61.69	gold quality
cerebellar vermis	UBERON:0004720	61.67	gold quality
triceps brachii	UBERON:0001509	61.44	gold quality
gluteal muscle	UBERON:0002000	61.40	gold quality
endothelial cell	CL:0000115	60.82	gold quality
cartilage tissue	UBERON:0002418	60.77	gold quality
deltoid	UBERON:0001476	60.50	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-3929	yes	260.86
E-MTAB-9388	yes	13.10
E-ANND-3	yes	5.25
E-MTAB-6819	no	642.93
E-MTAB-7008	no	413.76
E-ENAD-17	no	72.43
E-MTAB-9801	no	3.03

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

73 targeting HHLA1, 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-513A-5P	100.00	69.77	2465
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-370-5P	99.78	66.81	706
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-10393-5P	99.65	68.01	1368
HSA-MIR-298	99.63	67.56	1916
HSA-MIR-6513-3P	99.59	69.77	1102
HSA-MIR-3682-3P	99.58	67.63	865
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-516B-5P	99.56	66.33	1495
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-4452	99.50	68.45	1493
HSA-MIR-508-5P	99.41	64.25	1248
HSA-MIR-103A-1-5P	99.39	67.78	1545
HSA-MIR-103A-2-5P	99.39	67.72	1577

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Hhla1	ENSMUSG00000072511
rattus_norvegicus	Hhla1	ENSRNOG00000054588

Protein

Protein identifiers

HERV-H LTR-associating protein 1 — C9JL84 (reviewed: C9JL84)

All UniProt accessions (2): C9JL84, A0A5F9ZHM0

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Secreted.

Miscellaneous. Expressed in teratocarcinoma cell lines.

Isoforms (2)

UniProt ID	Names	Canonical?
C9JL84-1	1	yes
C9JL84-2	2, PLA2L

RefSeq proteins (1): NP_001138567* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR037643	HHLA1	Family

UniProt features (11 total): glycosylation site 3, region of interest 2, compositionally biased region 2, signal peptide 1, chain 1, sequence conflict 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-C9JL84-F1	43.86	0.00

Functional residue map

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

Glycosylation sites (3): 79, 143, 161

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 30 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, KIM_GASTRIC_CANCER_CHEMOSENSITIVITY, chr8q24, DCA_UP.V1_UP, KRAS.AMP.LUNG_UP.V1_DN, KRAS.600.LUNG.BREAST_UP.V1_DN, KRAS.BREAST_UP.V1_DN, KRAS.LUNG.BREAST_UP.V1_DN, MIR513A_5P, MIR6830_3P, MIR603, MIR103A_2_5P, MIR103A_1_5P, MIR7109_3P, DESCARTES_FETAL_CEREBRUM_MEGAKARYOCYTES

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (1): extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	1

Protein interactions and networks

STRING

508 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HHLA1	OC90	Q02509	970
HHLA1	FAM120A2P	Q5T035	583
HHLA1	AFDN	P55196	549
HHLA1	PLA2G2A	P14555	549
HHLA1	C4orf51	C9J302	530
HHLA1	ST6GAL1	P15907	491
HHLA1	ANKRD13C-DT	Q9XRX5	479
HHLA1	HLA-A	P01891	427
HHLA1	H7C0V5	H7C0V5	411
HHLA1	ABHD12B	Q7Z5M8	407
HHLA1	MAGEB5	Q9BZ81	399
HHLA1	KLHL23	Q8NBE8	394
HHLA1	TSNAX	Q99598	384
HHLA1	GOLGA8M	H3BSY2	357
HHLA1	RBM6	P78332	348

IntAct

0 interactions, top by confidence:

BioGRID (2): HHLA1 (Affinity Capture-MS), HHLA1 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A2R8Y7Y5, A1KXC4, A6QLF8, C9JL84, E9Q7X6, I3L273, J3KML8, O00592, O14594, O35188, O55145, O57604, O60667, O95196, P06484, P07141, P09603, P13838, P15702, P16150, P55067, P59647, P78423, Q1ECS6, Q28645, Q2TA21, Q2TB54, Q3TNW5, Q3TYV2, Q4V7A5, Q52S86, Q58Y74, Q5IS41, Q5M871, Q5SWP3, Q6MG22, Q6NXZ1, Q6UXF1, Q71M36, Q7Z434

Diamond homologs: C9JL84, Q3TYV2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	87
Likely benign	9
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2558 predictions. Top by Δscore:

Variant	Effect	Δscore
8:132076049:ACTT:A	donor_loss	1.0000
8:132076050:CTT:C	donor_loss	1.0000
8:132076051:TTA:T	donor_loss	1.0000
8:132076052:TA:T	donor_loss	1.0000
8:132076053:A:AC	donor_gain	1.0000
8:132076053:ACT:A	donor_loss	1.0000
8:132076053:ACTTG:A	donor_loss	1.0000
8:132076054:C:CC	donor_gain	1.0000
8:132076054:C:CG	donor_loss	1.0000
8:132087645:GTACT:G	donor_loss	1.0000
8:132087647:ACTC:A	donor_loss	1.0000
8:132087648:CT:C	donor_loss	1.0000
8:132087649:T:TA	donor_loss	1.0000
8:132087650:C:CG	donor_loss	1.0000
8:132087651:A:AC	donor_gain	1.0000
8:132087651:AC:A	donor_gain	1.0000
8:132087652:C:CA	donor_loss	1.0000
8:132087652:C:CC	donor_gain	1.0000
8:132087652:CC:C	donor_gain	1.0000
8:132089599:TC:T	acceptor_loss	1.0000
8:132089600:C:CA	acceptor_loss	1.0000
8:132089600:C:CC	acceptor_gain	1.0000
8:132095701:A:AC	donor_gain	1.0000
8:132095702:C:CC	donor_gain	1.0000
8:132076470:CTCA:C	donor_loss	0.9900
8:132076471:TCA:T	donor_loss	0.9900
8:132076472:CA:C	donor_loss	0.9900
8:132076473:ACCTG:A	donor_loss	0.9900
8:132076474:C:CG	donor_loss	0.9900
8:132076539:TGCTC:T	acceptor_gain	0.9900

AlphaMissense

3443 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:132087866:A:G	C190R	0.989
8:132087864:A:C	C190W	0.985
8:132064024:A:G	C523R	0.983
8:132065944:C:A	W498C	0.981
8:132065944:C:G	W498C	0.981
8:132065918:C:G	C507S	0.980
8:132065919:A:T	C507S	0.980
8:132071393:G:C	F472L	0.980
8:132071393:G:T	F472L	0.980
8:132071395:A:G	F472L	0.980
8:132087865:C:T	C190Y	0.980
8:132064023:C:G	C523S	0.978
8:132064024:A:T	C523S	0.978
8:132065919:A:G	C507R	0.977
8:132095547:A:C	C140W	0.977
8:132064008:C:G	C528S	0.976
8:132064009:A:T	C528S	0.976
8:132065917:A:C	C507W	0.976
8:132071401:A:G	C470R	0.976
8:132087865:C:G	C190S	0.976
8:132087866:A:T	C190S	0.976
8:132095553:G:C	C138W	0.976
8:132065941:A:C	F499L	0.975
8:132065941:A:T	F499L	0.975
8:132065943:A:G	F499L	0.975
8:132065962:A:C	C492W	0.975
8:132095555:A:G	C138R	0.975
8:132095758:A:C	S103R	0.975
8:132095758:A:T	S103R	0.975
8:132095760:T:G	S103R	0.975

dbSNP variants (sampled 300 via entrez): RS1000049630 (8:132111591 A>T), RS1000051071 (8:132100267 C>A), RS1000080494 (8:132100038 C>T), RS1000086107 (8:132075761 C>A,T), RS1000123705 (8:132062567 C>T), RS1000155567 (8:132088934 C>T), RS1000225643 (8:132071488 G>A), RS1000354846 (8:132105437 C>G), RS1000411846 (8:132062207 C>G), RS1000417777 (8:132100190 A>G,T), RS1000543411 (8:132084470 C>G,T), RS1000614758 (8:132085382 G>A,C), RS1000622471 (8:132078306 G>C,T), RS1000623878 (8:132079237 C>A), RS1000674972 (8:132078104 G>A,T)

Disease associations

OMIM: gene MIM:604109 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

3 total (human), top 3 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Allergens	increases expression	1
Benzo(a)pyrene	affects methylation	1
Cadmium Chloride	increases expression	1

Clinical trials (associated diseases)

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