HIGD2B

Summary

HIGD2B (HIG1 hypoxia inducible domain family member 2B, HGNC:26984) is a protein-coding gene on chromosome 15q24.1, encoding HIG1 domain family member 2B (Q4VC39).

Predicted to be involved in mitochondrial respirasome assembly. Predicted to be located in membrane. Predicted to be active in mitochondrion.

Source: NCBI Gene 123346 — RefSeq curated summary.

At a glance

• MANE Select transcript: NM_001350932

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26984
Approved symbol	HIGD2B
Name	HIG1 hypoxia inducible domain family member 2B
Location	15q24.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000175202
Ensembl biotype	protein_coding
Entrez	123346

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000311755, ENST00000911655

RefSeq mRNA: 1 — MANE Select: NM_001350932 NM_001350932

CCDS: CCDS86473

Canonical transcript exons

ENST00000311755 — 3 exons

Exon	Start	End
ENSE00001211074	72675798	72676387
ENSE00001340088	72680015	72680193
ENSE00001340091	72685818	72686182

Expression profiles

Bgee: expression breadth tissue_specific, 10 present calls, max score 91.09.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0213 / max 5.4760, expressed in 7 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
150840	0.0213	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.09	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.99	gold quality
testis	UBERON:0000473	63.61	gold quality
left testis	UBERON:0004533	63.39	gold quality
right testis	UBERON:0004534	62.30	gold quality
bone marrow cell	CL:0002092	42.18	gold quality
colonic epithelium	UBERON:0000397	41.63	gold quality
ganglionic eminence	UBERON:0004023	37.36	silver quality
sural nerve	UBERON:0015488	36.93	gold quality
granulocyte	CL:0000094	36.86	gold quality
apex of heart	UBERON:0002098	36.85	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	35.01	gold quality
skeletal muscle tissue	UBERON:0001134	34.82	gold quality
bone marrow	UBERON:0002371	34.82	gold quality
right uterine tube	UBERON:0001302	32.23	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
muscle tissue	UBERON:0002385	32.12	gold quality
blood	UBERON:0000178	30.93	gold quality
prefrontal cortex	UBERON:0000451	30.41	gold quality
lymph node	UBERON:0000029	30.04	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
vermiform appendix	UBERON:0001154	29.64	gold quality
adult mammalian kidney	UBERON:0000082	29.07	gold quality
tonsil	UBERON:0002372	29.06	gold quality
right lobe of liver	UBERON:0001114	28.96	gold quality
right adrenal gland cortex	UBERON:0035827	28.89	gold quality
body of pancreas	UBERON:0001150	28.45	gold quality
kidney	UBERON:0002113	28.20	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.47

Regulation

Is transcription factor: no

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	higd2a	ENSDARG00000052371
mus_musculus	Higd2a	ENSMUSG00000025868
rattus_norvegicus	AABR07035091.1	ENSRNOG00000001071
rattus_norvegicus	Higd2a	ENSRNOG00000017372

Paralogs (4): HIGD1B (ENSG00000131097), HIGD2A (ENSG00000146066), HIGD1A (ENSG00000181061), HIGD1C (ENSG00000214511)

Protein

Protein identifiers

HIG1 domain family member 2B — Q4VC39 (reviewed: Q4VC39)

All UniProt accessions (1): Q4VC39

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

RefSeq proteins (1): NP_001337861* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007667	Hypoxia_induced_domain	Domain
IPR050355	RCF1	Family

Pfam: PF04588

UniProt features (7 total): topological domain 3, transmembrane region 2, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q4VC39-F1	60.38	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 23 (showing top): GOBP_MITOCHONDRIAL_RESPIRATORY_CHAIN_COMPLEX_ASSEMBLY, ARID5B_TARGET_GENES, ATF6_TARGET_GENES, SETD7_TARGET_GENES, UBN1_TARGET_GENES, ZBTB18_TARGET_GENES, ZNF22_TARGET_GENES, ZNF257_TARGET_GENES, ZNF423_TARGET_GENES, GOBP_MITOCHONDRION_ORGANIZATION, ZSCAN31_TARGET_GENES, GOBP_MITOCHONDRIAL_RESPIRASOME_ASSEMBLY, MZF1_TARGET_GENES, HOXA1_TARGET_GENES, BRCA2_TARGET_GENES

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

GO Molecular Function (1): protein binding (GO:0005515)

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
binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

372 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HIGD2B	CCDC28A-AS1	A0A096LPI5	647
HIGD2B	DRICH1	Q6PGQ1	536
HIGD2B	C16orf89	Q6UX73	532
HIGD2B	C9orf85	Q96MD7	500
HIGD2B	GLRA3	O75311	467
HIGD2B	PLK5	Q496M5	455
HIGD2B	DHFR2	Q86XF0	453
HIGD2B	FAM218A	Q96MZ4	447
HIGD2B	PRR20A	P86496	435
HIGD2B	OR2T8	A6NH00	417
HIGD2B	STATH	P02808	380
HIGD2B	HTN3	P15516	380
HIGD2B	PRAMEF2	O60811	368
HIGD2B	ZFP62	Q8NB50	350
HIGD2B	COX7A2L	O14548	332

IntAct

10 interactions, top by confidence:

A	B	Type	Score
POU4F2	HIGD2B	psi-mi:“MI:0915”(physical association)	0.560
	HIGD2B	psi-mi:“MI:0915”(physical association)	0.560
HIGD2B	GPSM3	psi-mi:“MI:0915”(physical association)	0.560
POU4F2	HIGD2B	psi-mi:“MI:0915”(physical association)	0.000
GPSM3	HIGD2B	psi-mi:“MI:0915”(physical association)	0.000
	HIGD2B	psi-mi:“MI:0915”(physical association)	0.000

ESM2 similar proteins: A1XQS2, A4IJ20, F6QZ15, O14548, O60397, P0CU26, P13183, P14406, P24310, P34660, P46269, P56392, Q0V9J0, Q17ED3, Q290M9, Q2KI08, Q2M2S2, Q3T061, Q4QQV3, Q4R6H1, Q4VC39, Q5R504, Q5RE99, Q5REP2, Q5XIJ4, Q5XKA2, Q5ZML6, Q61387, Q64445, Q7JX57, Q7QHP6, Q7SXI1, Q7Z4L0, Q8BGY7, Q8BTC1, Q91W29, Q91Y94, Q99KD6, Q9BUB7, Q9BVV7

Diamond homologs: 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, C4JHR1, C4QV79, C4Y631, C4YRP9, C5DLZ7, C5DWC4, C5FSQ7, C5GDJ2, C5JIT3, C5MAV2, C5P447, C6H220, C7GT60

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

692 predictions. Top by Δscore:

Variant	Effect	Δscore
15:72680013:A:AC	donor_gain	1.0000
15:72680014:C:CC	donor_gain	1.0000
15:72680194:C:CC	acceptor_gain	1.0000
15:72683204:CA:C	donor_gain	1.0000
15:72680009:ACT:A	donor_loss	0.9900
15:72680010:CT:C	donor_loss	0.9900
15:72680011:TTACA:T	donor_loss	0.9900
15:72680012:T:TG	donor_loss	0.9900
15:72680013:A:C	donor_loss	0.9900
15:72680014:CA:C	donor_gain	0.9900
15:72680014:CAT:C	donor_gain	0.9900
15:72680191:TAG:T	acceptor_gain	0.9900
15:72680205:G:C	acceptor_gain	0.9900
15:72683203:A:AC	donor_gain	0.9900
15:72683204:C:CC	donor_gain	0.9900
15:72683303:AACT:A	acceptor_gain	0.9900
15:72683304:ACT:A	acceptor_gain	0.9900
15:72683305:C:CC	acceptor_gain	0.9900
15:72683306:T:A	acceptor_gain	0.9900
15:72680009:A:AC	donor_gain	0.9800
15:72680010:C:CC	donor_gain	0.9800
15:72680014:CATG:C	donor_gain	0.9800
15:72680191:TAGC:T	acceptor_loss	0.9800
15:72680193:GCTA:G	acceptor_loss	0.9800
15:72680194:CTAGA:C	acceptor_loss	0.9800
15:72680205:G:GC	acceptor_gain	0.9800
15:72683302:TAAC:T	acceptor_gain	0.9800
15:72683305:CTGA:C	acceptor_gain	0.9800
15:72680192:AG:A	acceptor_gain	0.9700
15:72683301:GTAAC:G	acceptor_gain	0.9700

AlphaMissense

687 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000584382 (15:72686720 C>T), RS1000674869 (15:72678711 A>G), RS1000768391 (15:72678903 A>G), RS1000790917 (15:72676407 G>T), RS1000835368 (15:72681492 A>G), RS1000986621 (15:72688076 ACTT>A), RS1001059526 (15:72686390 C>T), RS1001272091 (15:72679821 A>G), RS1001318298 (15:72686473 C>G,T), RS1001370900 (15:72686251 G>A,C), RS1001514468 (15:72678594 G>A), RS1001618637 (15:72680055 T>C), RS1002008941 (15:72685887 C>G), RS1002768425 (15:72681886 C>T), RS1002887842 (15:72678534 A>T)

Disease associations

OMIM: gene `` | 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

4 total (human), top 4 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
benzo(e)pyrene	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, affects response to substance, increases expression	1
Lipopolysaccharides	affects response to substance, increases expression, affects cotreatment	1
Methapyrilene	increases methylation	1

Clinical trials (associated diseases)

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