HIGD1B

Summary

HIGD1B (HIG1 hypoxia inducible domain family member 1B, HGNC:24318) is a protein-coding gene on chromosome 17q21.31, encoding HIG1 domain family member 1B (Q9P298).

This gene encodes a member of the hypoxia inducible gene 1 (HIG1) domain family. The encoded protein is localized to the cell membrane and has been linked to tumorigenesis and the progression of pituitary adenomas. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 51751 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 21 total
• MANE Select transcript: NM_016438

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24318
Approved symbol	HIGD1B
Name	HIG1 hypoxia inducible domain family member 1B
Location	17q21.31
Locus type	gene with protein product
Status	Approved
Aliases	CLST11240, CLST11240-15
Ensembl gene	ENSG00000131097
Ensembl biotype	protein_coding
OMIM	620420
Entrez	51751

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 8 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000253410, ENST00000586911, ENST00000587021, ENST00000590423, ENST00000591513, ENST00000856247, ENST00000856248, ENST00000856249, ENST00000923560, ENST00000954975

RefSeq mRNA: 2 — MANE Select: NM_016438 NM_001271880, NM_016438

CCDS: CCDS11488

Canonical transcript exons

ENST00000253410 — 3 exons

Exon	Start	End
ENSE00000897973	44849254	44849388
ENSE00001134786	44847883	44848252
ENSE00003465229	44850332	44850476

Expression profiles

Bgee: expression breadth ubiquitous, 206 present calls, max score 97.10.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.4464 / max 47.3776, expressed in 138 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
161195	0.1771	98
161196	0.1445	80
161194	0.1140	27
161193	0.0108	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	97.10	gold quality
right lung	UBERON:0002167	93.74	gold quality
upper lobe of left lung	UBERON:0008952	90.81	gold quality
heart left ventricle	UBERON:0002084	90.67	gold quality
putamen	UBERON:0001874	90.50	gold quality
cardiac ventricle	UBERON:0002082	90.31	gold quality
upper lobe of lung	UBERON:0008948	90.02	gold quality
caudate nucleus	UBERON:0001873	89.74	gold quality
anterior cingulate cortex	UBERON:0009835	89.70	gold quality
cingulate cortex	UBERON:0003027	89.61	gold quality
amygdala	UBERON:0001876	88.94	gold quality
right frontal lobe	UBERON:0002810	87.46	gold quality
nucleus accumbens	UBERON:0001882	87.36	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	86.78	gold quality
prefrontal cortex	UBERON:0000451	85.97	gold quality
substantia nigra	UBERON:0002038	85.90	gold quality
endothelial cell	CL:0000115	85.58	gold quality
lung	UBERON:0002048	85.44	gold quality
hypothalamus	UBERON:0001898	84.97	gold quality
medial globus pallidus	UBERON:0002477	84.69	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	84.52	gold quality
hindlimb stylopod muscle	UBERON:0004252	84.18	gold quality
spinal cord	UBERON:0002240	84.12	gold quality
Brodmann (1909) area 9	UBERON:0013540	84.10	gold quality
midbrain	UBERON:0001891	83.91	gold quality
telencephalon	UBERON:0001893	83.75	gold quality
gall bladder	UBERON:0002110	83.64	gold quality
gastrocnemius	UBERON:0001388	83.63	gold quality
neocortex	UBERON:0001950	83.58	gold quality
frontal cortex	UBERON:0001870	83.30	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-CURD-126	yes	2547.12
E-GEOD-124263	yes	1242.86
E-MTAB-8381	yes	985.68
E-MTAB-6308	yes	982.75
E-HCAD-1	yes	485.46
E-MTAB-8410	yes	19.03
E-GEOD-134144	yes	11.07
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 3)

• HIGD1B inhibits hypoxiainduced mitochondrial fragmentation by regulating OPA1 cleavage in cardiomyocytes. (PMID:34080026)
• Downregulation of HIGD1B induces mitochondria-mediated apoptosis in gastric cancer cells by inactivating Akt and ERK pathways. (PMID:38863387)
• HIGD1B, as a novel prognostic biomarker, is involved in regulating the tumor microenvironment and immune cell infiltration; its overexpression leads to poor prognosis in gastric cancer patients. (PMID:39108265)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	higd1a	ENSDARG00000022303
mus_musculus	Higd1b	ENSMUSG00000020928
rattus_norvegicus	Higd1b	ENSRNOG00000081879
drosophila_melanogaster	CG11825	FBGN0033519

Paralogs (4): HIGD2A (ENSG00000146066), HIGD2B (ENSG00000175202), HIGD1A (ENSG00000181061), HIGD1C (ENSG00000214511)

Protein

Protein identifiers

HIG1 domain family member 1B — Q9P298 (reviewed: Q9P298)

Alternative names: Protein CLST 11240

All UniProt accessions (3): Q9P298, K7EID5, K7EKK1

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

RefSeq proteins (2): NP_001258809, NP_057522* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007667	Hypoxia_induced_domain	Domain
IPR050355	RCF1	Family

Pfam: PF04588

UniProt features (14 total): topological domain 3, helix 3, strand 2, transmembrane region 2, sequence variant 2, chain 1, domain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2LON	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9P298-F1	67.42	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 71 (showing top): GOBP_MITOCHONDRIAL_RESPIRATORY_CHAIN_COMPLEX_ASSEMBLY, CAGCTG_AP4_Q5, NAKAMURA_LUNG_CANCER_DIFFERENTIATION_MARKERS, NKX25_01, TGGAAA_NFAT_Q4_01, NAKAMURA_ALVEOLAR_EPITHELIUM, LEE_BMP2_TARGETS_UP, PRC2_SUZ12_UP.V1_UP, NFE2L2.V2, ZNF596_TARGET_GENES, GOBP_MITOCHONDRION_ORGANIZATION, GSE13484_12H_UNSTIM_VS_YF17D_VACCINE_STIM_PBMC_UP, GSE8685_IL2_ACT_IL2_STARVED_VS_IL21_ACT_IL2_STARVED_CD4_TCELL_DN, GOBP_MITOCHONDRIAL_RESPIRASOME_ASSEMBLY, GSE15659_TREG_VS_TCONV_UP

GO Biological Process (1): mitochondrial respirasome assembly (GO:0097250)

GO Molecular Function (0):

GO Cellular Component (2): mitochondrion (GO:0005739), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mitochondrion organization	1
mitochondrial respiratory chain complex assembly	1
cytoplasm	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

562 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HIGD1B	COX4I2	Q96KJ9	612
HIGD1B	MS4A15	Q8N5U1	502
HIGD1B	FAM162B	Q5T6X4	488
HIGD1B	GJA4	P35212	471
HIGD1B	PLXDC1	Q8IUK5	455
HIGD1B	CYTH3	O43739	436
HIGD1B	MYO1B	O43795	424
HIGD1B	COL13A1	Q5TAT6	407
HIGD1B	SLC16A12	Q6ZSM3	407
HIGD1B	LRRN4	Q8WUT4	403
HIGD1B	PDGFRB	P09619	397
HIGD1B	GPER1	Q99527	395
HIGD1B	G5EA03	G5EA03	377
HIGD1B	GPR146	Q96CH1	372
HIGD1B	PEAR1	Q5VY43	369

IntAct

2 interactions, top by confidence:

A	B	Type	Score
HIGD1B	MYZAP	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (1): HIGD1B (Two-hybrid)

ESM2 similar proteins: A0A1D8PI78, A1XQR6, A2RVP7, A4QNF3, B2RYW8, O44477, O48528, P0CR88, P0CR89, P25710, P32897, P60602, P60603, P63030, P63031, P79082, P87130, P87146, Q02889, Q12328, Q3SZV8, Q3ZCG2, Q4V7T9, Q54K35, Q54QM0, Q55GU4, Q5NVQ1, Q5TGZ0, Q6BT35, Q6BZY4, Q6CRJ6, Q6FT37, Q6NYD1, Q751T2, Q75E80, Q7KSC4, Q7TNS2, Q80W89, Q8HXG6, Q8IN78

Diamond homologs: A8MV81, C7YJ02, C9SF29, Q4VC39, Q5NVQ1, Q76I25, Q8VH49, Q99JY6, Q9BW72, Q9CQJ1, Q9JLR9, Q9P298, Q9Y241, A1CHC5, A1CXG2, A2QI79, A3LVL1, A4RI25, A5DHC2, A5E2M7, A6RBB3, A6SSX6, A6ZM32, A7F679, A7TFU8, A8P006, B0D4J7, B0Y606, B2WBP3, B3LLM2, B6H465, B6K2Z6, B6QHL8, B6QHL9, B8MJJ2, B8N9M0, B9WHT6, C0NUL6, C0RYW2, C1G794

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	17
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

512 predictions. Top by Δscore:

Variant	Effect	Δscore
17:44848249:ATAGG:A	donor_loss	1.0000
17:44848250:TAGGT:T	donor_loss	1.0000
17:44848251:AGG:A	donor_loss	1.0000
17:44848252:GGT:G	donor_loss	1.0000
17:44848253:G:GG	donor_gain	1.0000
17:44848254:T:A	donor_loss	1.0000
17:44846425:GG:G	donor_gain	0.9900
17:44846426:GG:G	donor_gain	0.9900
17:44850330:A:AC	acceptor_loss	0.9900
17:44850330:A:AG	acceptor_gain	0.9900
17:44850331:G:GA	acceptor_loss	0.9900
17:44850331:G:GG	acceptor_gain	0.9900
17:44846427:G:GG	donor_gain	0.9800
17:44848058:A:AG	acceptor_gain	0.9800
17:44848059:G:GG	acceptor_gain	0.9800
17:44848059:GACT:G	acceptor_gain	0.9800
17:44848221:G:GT	donor_gain	0.9800
17:44848248:TATAG:T	donor_gain	0.9800
17:44848249:ATAG:A	donor_gain	0.9800
17:44848250:TAG:T	donor_gain	0.9800
17:44848251:AG:A	donor_gain	0.9800
17:44848252:GG:G	donor_gain	0.9800
17:44849384:GCTAG:G	donor_gain	0.9800
17:44850327:C:G	acceptor_gain	0.9800
17:44850331:GGT:G	acceptor_gain	0.9800
17:44846423:TAGGG:T	donor_loss	0.9700
17:44846424:AGGG:A	donor_loss	0.9700
17:44846426:GGTAA:G	donor_loss	0.9700
17:44846428:TAAG:T	donor_loss	0.9700
17:44849251:CA:C	acceptor_loss	0.9700

AlphaMissense

631 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:44849265:T:C	C38R	0.969
17:44849364:T:C	C71R	0.964
17:44849374:G:A	G74D	0.958
17:44849338:T:C	I62T	0.950
17:44849262:G:C	G37R	0.942
17:44849263:G:A	G37D	0.942
17:44849373:G:C	G74R	0.941
17:44849254:G:A	G34D	0.939
17:44849356:C:A	A68E	0.925
17:44850332:G:A	G79D	0.924
17:44849338:T:G	I62S	0.912
17:44849388:G:C	G79R	0.912
17:44849360:G:C	Q69H	0.909
17:44849360:G:T	Q69H	0.909
17:44849259:G:A	G36R	0.903
17:44849259:G:C	G36R	0.903
17:44849355:G:C	A68P	0.899
17:44849368:C:A	A72E	0.897
17:44848250:T:A	I33K	0.892
17:44849338:T:A	I62N	0.892
17:44849377:C:A	A75E	0.889
17:44849335:T:C	L61P	0.886
17:44849371:T:A	V73E	0.885
17:44848224:G:C	K24N	0.883
17:44848224:G:T	K24N	0.883
17:44848252:G:C	G34R	0.883
17:44849361:G:C	A70P	0.882
17:44849347:G:C	R65P	0.877
17:44849278:C:A	A42E	0.876
17:44849383:T:A	M77K	0.866

dbSNP variants (sampled 300 via entrez): RS1000030781 (17:44844887 T>C), RS1000111504 (17:44848487 A>C), RS1001732173 (17:44843360 A>T), RS1002014366 (17:44847593 A>C), RS1002163240 (17:44843678 T>C), RS1002229286 (17:44843336 G>A), RS1003255421 (17:44850551 T>C), RS1003282877 (17:44846407 C>A,G,T), RS1003433381 (17:44845185 G>A), RS1003494245 (17:44846662 C>G,T), RS1004003827 (17:44849965 T>C), RS1004050021 (17:44844521 G>A), RS1004164778 (17:44844939 T>C), RS1004420593 (17:44848543 T>A), RS1004612359 (17:44842986 C>T)

Disease associations

OMIM: gene MIM:620420 | 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

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
beta-lapachone	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Antirheumatic Agents	increases expression	1

Clinical trials (associated diseases)

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