APOBEC3H

Summary

APOBEC3H (apolipoprotein B mRNA editing enzyme catalytic subunit 3H, HGNC:24100) is a protein-coding gene on chromosome 22q13.1, encoding DNA dC->dU-editing enzyme APOBEC-3H (Q6NTF7). DNA deaminase (cytidine deaminase) which acts as an inhibitor of retrovirus replication and retrotransposon mobility via deaminase-dependent and -independent mechanisms.

This gene encodes a member of the apolipoprotein B mRNA-editing enzyme catalytic polypeptide 3 family of proteins. The encoded protein is a cytidine deaminase that has antiretroviral activity by generating lethal hypermutations in viral genomes. Polymorphisms and alternative splicing in this gene influence its antiretroviral activity and are associated with increased resistence to human immunodeficiency virus type 1 infection in certain populations. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 164668 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 35 total
• MANE Select transcript: NM_181773

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24100
Approved symbol	APOBEC3H
Name	apolipoprotein B mRNA editing enzyme catalytic subunit 3H
Location	22q13.1
Locus type	gene with protein product
Status	Approved
Aliases	ARP10
Ensembl gene	ENSG00000100298
Ensembl biotype	protein_coding
OMIM	610976
Entrez	164668

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 retained_intron

ENST00000348946, ENST00000401756, ENST00000421988, ENST00000442487, ENST00000474235, ENST00000613677, ENST00000613996

RefSeq mRNA: 4 — MANE Select: NM_181773 NM_001166002, NM_001166003, NM_001166004, NM_181773

CCDS: CCDS13985, CCDS54530, CCDS54531, CCDS54532

Canonical transcript exons

ENST00000442487 — 5 exons

Exon	Start	End
ENSE00000654680	39101237	39101504
ENSE00000654681	39101918	39102042
ENSE00001336905	39100272	39100428
ENSE00001795946	39103689	39104067
ENSE00003721860	39097244	39097343

Expression profiles

Bgee: expression breadth ubiquitous, 126 present calls, max score 85.86.

FANTOM5 (CAGE): breadth broad, TPM avg 1.0789 / max 129.4535, expressed in 271 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
192316	0.5914	218
192315	0.3315	91
192314	0.1560	51

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	85.86	gold quality
mucosa of stomach	UBERON:0001199	73.95	gold quality
blood	UBERON:0000178	73.66	gold quality
lymph node	UBERON:0000029	71.42	gold quality
spleen	UBERON:0002106	69.55	gold quality
vermiform appendix	UBERON:0001154	68.57	gold quality
right uterine tube	UBERON:0001302	68.33	gold quality
gall bladder	UBERON:0002110	66.45	gold quality
smooth muscle tissue	UBERON:0001135	66.12	gold quality
right adrenal gland cortex	UBERON:0035827	65.97	gold quality
rectum	UBERON:0001052	65.93	gold quality
placenta	UBERON:0001987	65.60	gold quality
descending thoracic aorta	UBERON:0002345	65.09	gold quality
ectocervix	UBERON:0012249	64.84	gold quality
fallopian tube	UBERON:0003889	64.80	gold quality
tibial artery	UBERON:0007610	64.79	gold quality
popliteal artery	UBERON:0002250	64.73	gold quality
bone marrow	UBERON:0002371	64.43	gold quality
tibial nerve	UBERON:0001323	63.93	gold quality
upper lobe of left lung	UBERON:0008952	63.39	gold quality
right coronary artery	UBERON:0001625	63.26	gold quality
thoracic aorta	UBERON:0001515	62.88	gold quality
ascending aorta	UBERON:0001496	62.66	gold quality
right adrenal gland	UBERON:0001233	62.60	gold quality
left uterine tube	UBERON:0001303	62.20	gold quality
body of uterus	UBERON:0009853	61.40	gold quality
thoracic mammary gland	UBERON:0005200	61.36	gold quality
myometrium	UBERON:0001296	61.16	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	60.79	gold quality
cerebellar hemisphere	UBERON:0002245	60.74	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-8060	no	52.46
E-ANND-3	no	2.28

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

22 targeting APOBEC3H, 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-4481	100.00	66.42	1669
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-8076	99.78	68.52	1170
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-103A-1-5P	99.39	67.78	1545
HSA-MIR-103A-2-5P	99.39	67.72	1577
HSA-MIR-520F-5P	99.34	70.40	1632
HSA-MIR-7151-3P	99.04	69.72	2370
HSA-MIR-1227-5P	98.65	65.32	1549
HSA-MIR-4773	98.35	67.30	1710
HSA-MIR-3159	97.94	66.79	1098
HSA-MIR-890	97.47	68.67	982
HSA-MIR-526B-5P	97.41	67.99	1074
HSA-MIR-500B-3P	96.49	65.40	1087

Literature-anchored findings (GeneRIF, showing 40)

• A3H inhibits HIV-1 replication potently by a cytidine deamination-independent mechanism (PMID:18299330)
• study provides evidence of editing of human papillomavirus 1a and 16 DNA by APOBEC3 in plantar warts and precancerous cervix biopsies (PMID:18403710)
• These results indicate that APOBEC3G, APOBEC3C and APOBEC3H have the ability to edit HBV DNA and that each protein is likely to contribute to various degrees to the generation of modified genomes in human liver cells. (PMID:18420796)
• APOBEC3H antiviral activity has been lost in the majority of humans may have important consequences for our susceptibility to retroviral infections as well as ongoing retroelement proliferation in the human genome. (PMID:18779051)
• These observations suggest that human Z2-type cytidine deaminase A3H variants have varying intrinsic abilities to restrict retroelements and that various APOBEC3 proteins may have evolved distinct inhibitory mechanisms against retroelements. (PMID:18827027)
• the anti-HIV activity of APOBEC3H seems to be regulated by a combination of genomic variation and alternative splicing. (PMID:18945781)
• APOBEC3H is not as strong of a selective force for current HIV-1 infections as human APOBEC3G. (PMID:19828612)
• In contrast to APOBEC3H(A3H)_HapII, A3H_Haplotype I (HapI), which differs in only three amino acids from A3H_HapII, was resistant to HIV-1 Vif-mediated degradation. Residue 121 was critical for determining A3H sensitivity and binding to HIV-1 Vif. (PMID:19939923)
• These data show that the antiviral activity of APOBEC3H haplotypes is determined by its incorporation into the viral core, in proximity to the reverse transcription complex. (PMID:20519396)
• examined SNPs in APOBEC3 locus paired with sequences of proviral HIV-1 vif from HIV-1-infected adults; evidence for APOBEC3H linkage disequilibrium block associated with variation in GA –> AA, or APOBEC3F/H signature, sequence changes in proviral vif (PMID:21167246)
• The authors conclude that stably expressed APOBEC3H haplotypes may be more broadly distributed in humans than previously realized, and APOBEC3H protein is resistant to HIV-1 Vif. (PMID:21270145)
• APOBEC3H protein encoded by haplotype II is actively retained in the cytoplasm by interacting with speci fi c host factors, whereas the less active protein encoded by haplotype I is allowed to enter the nucleus by a passive mechanism (PMID:21653666)
• Most Vif proteins counteract APOBEC3G and APOBEC3F efficiently but display differences with respect to the inhibition of APOBEC3H. (PMID:22013041)
• A positively selected APOBEC3H haplotype is associated with natural resistance to HIV-1 infection. (PMID:22023594)
• The authors show that APOBEC3A, APOBEC3B, and APOBEC3H haplotype 2 (A3H hapII) acted as potent inhibitors of HTLV-1. (PMID:22457529)
• Amino acid changes within APOBEC3H can give rise to variants that are highly diverse in anti-viral activities and cellular localizations. (PMID:22859935)
• A3H-hapII is resistant to NL4-3 Vif while it is efficiently degraded by LAI Vif. (PMID:23469063)
• Taken together, these data validate APOBEC3H expressed at endogenous levels as a bona fide HIV-1 restriction factor. (PMID:24139399)
• APOBEC3 deaminases upregulated by IFN-beta induce E2 hypermutation of HPV16 in cervical keratinocytes. (PMID:24227842)
• stable APOBEC3H haplotypes present as in vivo barriers to HIV-1 replication, that Vif is capable of adapting to these restrictive pressures, and that an evolutionary equilibrium has yet to be reached. (PMID:25411794)
• The existence and persistence of both types of HIV-1 Vif variant suggests the importance of APOBEC3H suppression and cell cycle regulation for HIV-1’s survival in vivo. (PMID:25590520)
• Importantly, APOBEC3H appears to use both deaminase-dependent and -independent mechanisms to target reverse transcription and restrict HIV-1 replication. (PMID:25614027)
• A3H with low anti-HIV-1 activity, APOBEC3H-hapC, is associated with the susceptibility to HIV-1 infection, whereas the A3H producing a stable protein, A3H-hapB, may confer a low risk of disease progression to AIDS. (PMID:25721876)
• APOBEC3H haplotype II was able to processively deaminate multiple cytosines in a single enzyme-substrate encounter by using sliding, jumping, and intersegmental transfer movements. (PMID:26396192)
• The eQTL-missense polymorphisms of APOBEC3H are associated with lung cancer risk in a Han Chinese population (PMID:26459911)
• Haplotype analysis showed that the frequencies of 15del-105R was high (0.475 vs 0.400, OR=1.36, permutation P=0.037) in the HIV-1-infected subjects, confirming the association of A3H polymorphisms with the susceptibility to HIV-1 infection (PMID:26559750)
• These results indicate that APOBEC3 proteins can be copackaged and can comutate the same genomes, and can cooperate to inhibit HIV replication. (PMID:27439715)
• The deamination activity of these APOBEC3H variants correlates well with their reported anti-HIV activity for the different haplotypes, suggesting that deaminase activity may be an important factor in determining their respective anti-HIV activities. (PMID:27534815)
• These studies combine to suggest that A3B and A3H-I haplotypes, together, explain the bulk of ‘APOBEC signature’ mutations in cancer. (PMID:27650891)
• There are 10 APOBEC3H residues required for the HIV-1 Vif susceptibility and Vif binding. (PMID:28336404)
• Stable variants of APOBEC3H impose selective pressure on HIV-1. (PMID:28475648)
• we speculate that stably expressed human A3H protects humans against the cross-species transmission of zoonotic infection of SIV of chimpanzee (PMID:29267382)
• the results support a model in which structured RNA negatively regulates the potentially harmful DNA deamination activity of APOBEC3H while, at the same time, positively regulating its antiviral activity. (PMID:29290613)
• APOBEC3H role in the spontaneous control of HIV infection. (PMID:29333092)
• Structure, Multimerization, Subcellular Localization and mC Selectivity of a Genomic Mutator and Anti-HIV Factor APOBEC3H (PMID:29491387)
• we reveal the 2.20-A crystal structure of the chimpanzee A3H (cpzA3H) dimer bound to a short double-stranded RNA (dsRNA), which appears to be similar to two recently reported structures of pig-tailed macaque A3H and human A3H (PMID:30060196)
• APOBEC3A, APOBEC3B, and APOBEC3H, demonstrated the highest transcript expression in recessive dystrophic epidermolysis bullosa (RDEB) squamous cell carcinoma (SCC) compared with normal skin and for all SCC subtypes analyzed. Furthermore, the proportion of APOBEC mutations associated with APOBEC3A was greater than the context associated with APOBEC3B. (PMID:30135250)
• APOBEC3H has a structural zipcode for subcellular localization and selecting viral substrates for restriction. (PMID:30224517)
• Data show that splice variants SV200 is at least fourfold more HIV-1 restrictive than other apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3H APOBEC3H (A3H) splice variants. (PMID:30297863)
• Data demonstrate that the cellular RNA bound by APOBEC3H does not completely inhibit enzyme activity, in contrast to other APOBEC family members. Despite degradation of the cellular RNA, an approximately 12-nt RNA remains bound to the enzyme, even in the presence of ssDNA. The RNA-mediated dimer is disrupted by mutating W115 on loop 7 or R175 and R176 on helix 6, but this also disrupts protein stability. (PMID:30414963)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Apobec3	ENSMUSG00000009585
rattus_norvegicus	Apobec3	ENSRNOG00000016852

Paralogs (9): APOBEC1 (ENSG00000111701), AICDA (ENSG00000111732), APOBEC2 (ENSG00000124701), APOBEC3A (ENSG00000128383), APOBEC3F (ENSG00000128394), APOBEC3B (ENSG00000179750), APOBEC3G (ENSG00000239713), APOBEC3D (ENSG00000243811), APOBEC3C (ENSG00000244509)

Protein

Protein identifiers

DNA dC->dU-editing enzyme APOBEC-3H — Q6NTF7 (reviewed: Q6NTF7)

Alternative names: APOBEC-related protein 10, Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3H

All UniProt accessions (4): Q6NTF7, A0A087WZI3, B7TQM3, B7TQM4

UniProt curated annotations — full annotation on UniProt →

Function. DNA deaminase (cytidine deaminase) which acts as an inhibitor of retrovirus replication and retrotransposon mobility via deaminase-dependent and -independent mechanisms. The A3H-var/haplotype 2 exhibits antiviral activity against vif-deficient HIV-1. After the penetration of retroviral nucleocapsids into target cells of infection and the initiation of reverse transcription, it can induce the conversion of cytosine to uracil in the minus-sense single-strand viral DNA, leading to G-to-A hypermutations in the subsequent plus-strand viral DNA. The resultant detrimental levels of mutations in the proviral genome, along with a deamination-independent mechanism that works prior to the proviral integration, together exert efficient antiretroviral effects in infected target cells. Selectively targets single-stranded DNA and does not deaminate double-stranded DNA or single- or double-stranded RNA. Exhibits antiviral activity also against T-cell leukemia virus type 1 (HTLV-1) and may inhibit the mobility of LTR and non-LTR retrotransposons.

Subunit / interactions. Homodimer. Interacts with AGO1, AGO2 and AGO3.

Subcellular location. Cytoplasm. Nucleus. P-body.

Tissue specificity. Expressed in lymphoid organs. Also detected in non-lymphoid tissues including lung, testis, ovary, fetal liver and skin.

Post-translational modifications. (Microbial infection) Following infection by some HIV-1 strains, such as isolate BRU/LAI, can be ubiquitinated by a cullin-5-RING E3 ubiquitin-protein ligase complex (ECS complex) hijacked by the HIV-1 Vif protein, leading to its degradation. Ubiquitination by the ECS complex is however less efficent compared to APOBEC3G or APOBEC3G.

Activity regulation. APOBEC3H activity is regulated by RNA. While RNA-binding inhibits the DNA deaminase activity, double-stranded RNA is required for HIV-1 restriction by promoting APOBEC3H homodimerization and packaging into retroviral nucleocapsids. (Microbial infection) Antiviral activity is inhibited to some extent by the HIV-1 virion infectivity factor (VIF), that prevents its incorporation into progeny virions by both inhibiting its translation and/or by inducing its ubiquitination and subsequent degradation by the 26S proteasome.

Polymorphism. There are at least 4 different haplotypes in the human population. The allele A3H-var/haplotype 2 encodes a more stable protein which is able to block HIV-1 replication. The displayed allele (haplotype 1) is unstable and inefficient to block HIV-1 replication.

Miscellaneous. APOBEC3H from old world monkeys has retained its antiviral activity, while it is lost in other primates. It is one of seven related genes or pseudogenes found in a cluster, thought to result from gene duplication, on chromosome 22.

Similarity. Belongs to the cytidine and deoxycytidylate deaminase family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q6NTF7-1	1	yes
Q6NTF7-2	2
Q6NTF7-3	3
Q6NTF7-4	4

RefSeq proteins (4): NP_001159474, NP_001159475, NP_001159476, NP_861438* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002125	CMP_dCMP_dom	Domain
IPR016192	APOBEC/CMP_deaminase_Zn-bd	Binding_site
IPR016193	Cytidine_deaminase-like	Homologous_superfamily
IPR041512	APOBEC3H	Family
IPR050610	APOBEC_Cyt_Deaminase	Family

Pfam: PF18771

Enzyme classification (BRENDA):

• EC 3.5.4.38 — single-stranded DNA cytosine deaminase (BRENDA: 8 organisms, 58 substrates, 4 inhibitors, 11 Km, 10 kcat entries)

Substrate kinetics (BRENDA)

2 substrates with measured Km, best-characterized 2. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
CCCA	0.001–0.073	5
TTCA	0.001–0.019	5

Catalyzed reactions (Rhea), 1 shown:

• a 2’-deoxycytidine in single-stranded DNA + H2O + H(+) = a 2’-deoxyuridine in single-stranded DNA + NH4(+) (RHEA:50948)

UniProt features (65 total): mutagenesis site 32, strand 8, sequence variant 7, helix 6, binding site 3, splice variant 3, chain 1, domain 1, coiled-coil region 1, active site 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
5W45	X-RAY DIFFRACTION	2.49
8FVI	ELECTRON MICROSCOPY	3.24
6B0B	X-RAY DIFFRACTION	3.28
6BBO	X-RAY DIFFRACTION	3.43

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6NTF7-F1	89.41	0.79

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 (1): 56 (proton donor)

Ligand- & substrate-binding residues (3): 54; 85; 88

Mutagenesis-validated functional residues (32):

Position	Phenotype
18	increased dna deaminase activity.
20	increased dna deaminase activity.
21	decreased dna deaminase activity.
22	decreased dna deaminase activity.
23	decreased dna deaminase activity.
24	decreased dna deaminase activity.
25	decreased dna deaminase activity.
26	does not affect the dna deaminase activity.
50–51	does not affect ubiquitination by an ecs complex hijacked by hiv-1 vif.
50	does not affect the dna deaminase activity.
51	does not affect the dna deaminase activity.
52	does not affect the dna deaminase activity.
56	abolished dna deaminase activity.
56	reduces the ability to inhibit the retrotransposition of line-1 elements.
70	partial resistance to ubiquitination and degradation by an ecs complex hijacked by hiv-1 vif.
90	resistance to ubiquitination and degradation by an ecs complex hijacked by hiv-1 vif.
94	resistance to ubiquitination and degradation by an ecs complex hijacked by hiv-1 vif.
97	increased ubiquitination and degradation by an ecs complex hijacked by hiv-1 vif.
110	decreased dna deaminase activity.
111	decreased dna deaminase activity.
112	decreased dna deaminase activity.
113	decreased dna deaminase activity.
114	increased dna deaminase activity.
115	increased dna deaminase activity.
125	resistance to ubiquitination and degradation by an ecs complex hijacked by hiv-1 vif.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-72200	mRNA Editing: C to U Conversion
R-HSA-75094	Formation of the Editosome
R-HSA-75072	mRNA Editing
R-HSA-8953854	Metabolism of RNA

MSigDB gene sets: 63 (showing top): GOBP_NEGATIVE_REGULATION_OF_VIRAL_PROCESS, GOBP_MODULATION_OF_PROCESS_OF_ANOTHER_ORGANISM, GOBP_HOST_MEDIATED_PERTURBATION_OF_VIRAL_PROCESS, GOBP_DNA_MODIFICATION, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_RNA_MODIFICATION, GOBP_VIRAL_GENOME_REPLICATION, GOBP_VIRAL_LIFE_CYCLE, GOBP_DEFENSE_RESPONSE_TO_VIRUS, GOBP_REGULATION_OF_VIRAL_GENOME_REPLICATION, GOBP_NEGATIVE_REGULATION_OF_VIRAL_GENOME_REPLICATION, GOBP_RESPONSE_TO_VIRUS, REACTOME_METABOLISM_OF_RNA, GOCC_RIBONUCLEOPROTEIN_GRANULE, chr22q13

GO Biological Process (11): transposable element silencing (GO:0010526), cytidine to uridine editing (GO:0016554), clearance of foreign intracellular DNA (GO:0044355), host-mediated suppression of viral genome replication (GO:0044828), innate immune response (GO:0045087), negative regulation of single stranded viral RNA replication via double stranded DNA intermediate (GO:0045869), defense response to virus (GO:0051607), DNA cytosine deamination (GO:0070383), immune system process (GO:0002376), regulation of macromolecule biosynthetic process (GO:0010556), negative regulation of viral genome replication (GO:0045071)

GO Molecular Function (7): RNA binding (GO:0003723), cytidine deaminase activity (GO:0004126), zinc ion binding (GO:0008270), catalytic activity (GO:0003824), protein binding (GO:0005515), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (5): P-body (GO:0000932), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
mRNA Editing	1
mRNA Editing: C to U Conversion	1
Metabolism of RNA	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
viral genome replication	2
negative regulation of gene expression	1
retrotransposition	1
base conversion or substitution editing	1
clearance of foreign intracellular nucleic acids	1
host-mediated perturbation of viral process	1
immune response	1
defense response to symbiont	1
single stranded viral RNA replication via double stranded DNA intermediate	1
negative regulation of viral genome replication	1
regulation of single stranded viral RNA replication via double stranded DNA intermediate	1
negative regulation of RNA biosynthetic process	1
defense response	1
response to virus	1
DNA deamination	1
biological_process	1
macromolecule biosynthetic process	1
regulation of biosynthetic process	1
regulation of macromolecule metabolic process	1
regulation of viral genome replication	1
negative regulation of viral process	1
nucleic acid binding	1
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in cyclic amidines	1
deaminase activity	1
transition metal ion binding	1
molecular_function	1
binding	1
catalytic activity	1
cation binding	1
cytoplasmic ribonucleoprotein granule	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

762 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
APOBEC3H	CDA	P32320	868
APOBEC3H	APOBEC4	Q8WW27	838
APOBEC3H	CUL5	Q93034	657
APOBEC3H	UNG	P13051	597
APOBEC3H	ELOB	Q15370	583
APOBEC3H	CBFB	Q13951	581
APOBEC3H	APOB	P04114	545
APOBEC3H	ELOC	Q15369	532
APOBEC3H	TRIM5	Q9C035	527
APOBEC3H	APOBEC3B	Q9UH17	520
APOBEC3H	APOBEC3A	P31941	518
APOBEC3H	RNF7	Q9UBF6	510
APOBEC3H	CBX6	O95503	503
APOBEC3H	APOBEC3C	Q9NRW3	496
APOBEC3H	SAMHD1	Q9Y3Z3	466

IntAct

0 interactions, top by confidence:

BioGRID (7): APOBEC3H (Reconstituted Complex), APOBEC3H (Affinity Capture-MS), APOBEC3H (Affinity Capture-Western), VHL (Affinity Capture-Western), APOBEC3H (PCA), APOBEC3H (Biochemical Activity), APOBEC3H (Co-crystal Structure)

ESM2 similar proteins: A2VDP6, A9QA56, G1SRW8, P0C7P3, P31941, P60704, P60705, Q08AF3, Q19Q52, Q1WBT4, Q2PT36, Q3SYR3, Q4VDN5, Q5RCA5, Q5XI89, Q68D06, Q694B4, Q694B5, Q694B6, Q694B7, Q694B8, Q694B9, Q694C0, Q694C1, Q694C2, Q694C4, Q694C5, Q6NTF7, Q75W64, Q7YR23, Q7YR24, Q7YR25, Q7Z7L1, Q8IUX4, Q8IXQ6, Q969Y0, Q96AK3, Q99J72, Q9BQQ7, Q9GZX7

Diamond homologs: A9QA56, P31941, P38483, P41238, P47855, P60704, P60705, Q19Q52, Q1WBT4, Q2PT36, Q4VDN5, Q694B3, Q694B5, Q694B6, Q694B7, Q694B8, Q694B9, Q694C0, Q694C1, Q694C2, Q694C4, Q694C5, Q6NTF7, Q75W64, Q7YR23, Q7YR24, Q7YR25, Q8IUX4, Q99J72, Q9EQP0, Q9GZX7, Q9HC16, Q9NRW3, Q9TUI7, Q9UH17, Q9WVE0, Q3SYR3, Q694B4, Q96AK3, Q9WV35

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
APOBEC3H	up-regulates	“Clearance_of_foreign intracellular_DNA”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	26
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

761 predictions. Top by Δscore:

Variant	Effect	Δscore
22:39101505:G:GG	donor_gain	1.0000
22:39102039:AAAGG:A	donor_loss	1.0000
22:39102043:G:T	donor_loss	1.0000
22:39102044:T:A	donor_loss	1.0000
22:39100268:A:AG	acceptor_gain	0.9900
22:39100269:C:G	acceptor_gain	0.9900
22:39100270:A:AG	acceptor_gain	0.9900
22:39100271:G:GG	acceptor_gain	0.9900
22:39100271:GA:G	acceptor_gain	0.9900
22:39100271:GAAAC:G	acceptor_gain	0.9900
22:39100313:A:AG	acceptor_gain	0.9900
22:39100314:G:GG	acceptor_gain	0.9900
22:39100412:GC:G	donor_gain	0.9900
22:39101484:TGG:T	donor_gain	0.9900
22:39101486:G:GT	donor_gain	0.9900
22:39101510:A:T	donor_gain	0.9900
22:39101525:T:G	donor_gain	0.9900
22:39103688:GCA:G	acceptor_gain	0.9900
22:39097339:ATCAG:A	donor_loss	0.9800
22:39097340:TCAGG:T	donor_loss	0.9800
22:39097341:CAG:C	donor_loss	0.9800
22:39097342:AG:A	donor_loss	0.9800
22:39097343:GGTAC:G	donor_loss	0.9800
22:39097344:GTA:G	donor_loss	0.9800
22:39097345:T:A	donor_loss	0.9800
22:39100267:CACA:C	acceptor_loss	0.9800
22:39100268:ACAG:A	acceptor_loss	0.9800
22:39100270:A:G	acceptor_loss	0.9800
22:39100271:GAA:G	acceptor_gain	0.9800
22:39101222:T:A	acceptor_gain	0.9800

AlphaMissense

1204 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:39100315:T:C	F13L	0.978
22:39100317:T:A	F13L	0.978
22:39100317:T:G	F13L	0.978
22:39101920:T:C	F141L	0.968
22:39101922:T:A	F141L	0.968
22:39101922:T:G	F141L	0.968
22:39101941:T:C	F148L	0.968
22:39101943:T:A	F148L	0.968
22:39101943:T:G	F148L	0.968
22:39101333:A:C	S83R	0.964
22:39101335:C:A	S83R	0.964
22:39101335:C:G	S83R	0.964
22:39100303:T:C	F9L	0.957
22:39100305:C:A	F9L	0.957
22:39100305:C:G	F9L	0.957
22:39101405:T:C	F107L	0.928
22:39101407:C:A	F107L	0.928
22:39101407:C:G	F107L	0.928
22:39101262:T:C	F59S	0.905
22:39101494:G:A	M136I	0.897
22:39101494:G:C	M136I	0.897
22:39101494:G:T	M136I	0.897
22:39101921:T:G	F141C	0.896
22:39101403:T:C	I106T	0.884
22:39100316:T:C	F13S	0.876
22:39101369:T:C	F95L	0.876
22:39101371:C:A	F95L	0.876
22:39101371:C:G	F95L	0.876
22:39101318:T:C	C78R	0.875
22:39101261:T:C	F59L	0.867

dbSNP variants (sampled 300 via entrez): RS1000247179 (22:39100498 T>G), RS1000653300 (22:39101752 T>C,G), RS1000750778 (22:39096533 G>A,C), RS1000762900 (22:39097695 A>T), RS1000818144 (22:39095299 T>C), RS1001145393 (22:39099257 A>G), RS1001213185 (22:39098382 C>T), RS1001423332 (22:39103835 A>C), RS1001665899 (22:39098728 C>T), RS1002941748 (22:39099823 C>G), RS1003111913 (22:39102099 T>A,C), RS1003274950 (22:39100798 T>C), RS1003543887 (22:39098248 G>A,C), RS1003754968 (22:39095383 C>G), RS1003835554 (22:39103692 T>C)

Disease associations

OMIM: gene MIM:610976 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90002393_590	Monocyte count	2.000000e-18

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005091	monocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
propionaldehyde	increases expression	1
aflatoxin B2	increases methylation	1
di-n-butylphosphoric acid	affects expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Caffeine	decreases phosphorylation	1
Cisplatin	increases expression	1
Diuron	decreases expression	1
Silicon Dioxide	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	increases methylation	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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