ADAD2

Summary

ADAD2 (adenosine deaminase domain containing 2, HGNC:30714) is a protein-coding gene on chromosome 16q24.1, encoding Adenosine deaminase domain-containing protein 2 (Q8NCV1). Required for male fertility and normal male germ cell differentiation.

Predicted to enable double-stranded RNA adenosine deaminase activity; double-stranded RNA binding activity; and tRNA-specific adenosine deaminase activity. Predicted to be involved in RNA processing; adenosine to inosine editing; and spermatid development. Predicted to be located in nucleus. Predicted to be active in cytoplasm and nucleolus.

Source: NCBI Gene 161931 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 209 total — 8 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_001145400

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30714
Approved symbol	ADAD2
Name	adenosine deaminase domain containing 2
Location	16q24.1
Locus type	gene with protein product
Status	Approved
Aliases	TENRL, FLJ00337
Ensembl gene	ENSG00000140955
Ensembl biotype	protein_coding
OMIM	619532
Entrez	161931

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 5 protein_coding, 5 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000268624, ENST00000315906, ENST00000563849, ENST00000564169, ENST00000564430, ENST00000566526, ENST00000567413, ENST00000567685, ENST00000569221, ENST00000922036, ENST00000922037

RefSeq mRNA: 2 — MANE Select: NM_001145400 NM_001145400, NM_139174

CCDS: CCDS10944, CCDS45536

Canonical transcript exons

ENST00000315906 — 10 exons

Exon	Start	End
ENSE00001190919	84191157	84191648
ENSE00003470378	84194933	84194980
ENSE00003477956	84196647	84196767
ENSE00003478414	84196127	84196370
ENSE00003534095	84195296	84195446
ENSE00003549852	84194442	84194582
ENSE00003658585	84195530	84195697
ENSE00003689977	84195815	84196044
ENSE00003692159	84195069	84195194
ENSE00003904079	84196870	84197166

Expression profiles

Bgee: expression breadth ubiquitous, 168 present calls, max score 97.50.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2216 / max 171.4123, expressed in 14 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
155301	0.1044	6
155299	0.0474	8
155302	0.0234	5
155300	0.0212	4
155297	0.0115	3
155298	0.0082	4
155303	0.0055	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	97.50	gold quality
left testis	UBERON:0004533	97.23	gold quality
testis	UBERON:0000473	94.50	gold quality
pigmented layer of retina	UBERON:0001782	88.29	gold quality
retina	UBERON:0000966	88.27	gold quality
epithelial cell of pancreas	CL:0000083	87.25	gold quality
oocyte	CL:0000023	86.12	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.93	gold quality
sperm	CL:0000019	83.34	silver quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	81.38	silver quality
pancreatic ductal cell	CL:0002079	80.98	silver quality
vena cava	UBERON:0004087	80.55	silver quality
upper arm skin	UBERON:0004263	80.11	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.75	gold quality
lower esophagus mucosa	UBERON:0035834	76.87	gold quality
esophagus mucosa	UBERON:0002469	76.17	gold quality
spleen	UBERON:0002106	75.99	gold quality
secondary oocyte	CL:0000655	75.70	gold quality
nasal cavity epithelium	UBERON:0005384	75.41	gold quality
esophagus squamous epithelium	UBERON:0006920	74.36	silver quality
tendon of biceps brachii	UBERON:0008188	73.28	silver quality
layer of synovial tissue	UBERON:0007616	73.14	silver quality
pharyngeal mucosa	UBERON:0000355	73.05	gold quality
inferior vagus X ganglion	UBERON:0005363	72.82	silver quality
superficial temporal artery	UBERON:0001614	72.75	gold quality
pericardium	UBERON:0002407	72.73	silver quality
kidney epithelium	UBERON:0004819	72.73	gold quality
synovial joint	UBERON:0002217	72.57	gold quality
saphenous vein	UBERON:0007318	72.41	silver quality
cerebellar vermis	UBERON:0004720	72.28	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-135922	yes	13.30
E-CURD-10	no	20.06
E-ANND-3	no	1.99

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

3 targeting ADAD2, 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-3682-5P	99.93	67.97	1163
HSA-MIR-361-3P	99.19	66.45	1381
HSA-MIR-4268	94.45	64.09	819

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	adad2	ENSDARG00000105626
mus_musculus	Adad2	ENSMUSG00000024266
rattus_norvegicus	Adad2	ENSRNOG00000015690
drosophila_melanogaster	Adar	FBGN0026086
drosophila_melanogaster	Adat1	FBGN0028658
drosophila_melanogaster	loqs	FBGN0032515
drosophila_melanogaster	CG12493	FBGN0035571
drosophila_melanogaster	blanks	FBGN0035608
drosophila_melanogaster	Zn72D	FBGN0263603
caenorhabditis_elegans		WBGENE00018857
caenorhabditis_elegans	zfr-1	WBGENE00022388

Paralogs (14): STAU2 (ENSG00000040341), ZFR (ENSG00000056097), ADAT1 (ENSG00000065457), ZFR2 (ENSG00000105278), STAU1 (ENSG00000124214), ILF3 (ENSG00000129351), TARBP2 (ENSG00000139546), ILF2 (ENSG00000143621), ADAR (ENSG00000160710), ADAD1 (ENSG00000164113), STRBP (ENSG00000165209), PRKRA (ENSG00000180228), ADARB2 (ENSG00000185736), ADARB1 (ENSG00000197381)

Protein

Protein identifiers

Adenosine deaminase domain-containing protein 2 — Q8NCV1 (reviewed: Q8NCV1)

Alternative names: Testis nuclear RNA-binding protein-like

All UniProt accessions (2): Q8NCV1, H3BNP6

UniProt curated annotations — full annotation on UniProt →

Function. Required for male fertility and normal male germ cell differentiation.

Subcellular location. Nucleus. Cytoplasm.

Similarity. Belongs to the ADAD family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8NCV1-1	1	yes
Q8NCV1-2	2

RefSeq proteins (2): NP_001138872, NP_631913 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002466	A_deamin	Domain
IPR014720	dsRBD_dom	Domain
IPR044454	ADAD2_DSRM	Domain

Pfam: PF00035, PF02137

UniProt features (9 total): sequence variant 3, domain 2, splice variant 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NCV1-F1	76.35	0.44

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 39 (showing top): GOBP_MALE_GAMETE_GENERATION, GOBP_RNA_MODIFICATION, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GOCC_NUCLEOLUS, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_CARBON_NITROGEN_BUT_NOT_PEPTIDE_BONDS_IN_CYCLIC_AMIDINES, GOMF_ADENOSINE_DEAMINASE_ACTIVITY, GOMF_DEAMINASE_ACTIVITY, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_CARBON_NITROGEN_BUT_NOT_PEPTIDE_BONDS, GOBP_ADENOSINE_TO_INOSINE_EDITING, GOBP_BASE_CONVERSION_OR_SUBSTITUTION_EDITING, GOMF_DOUBLE_STRANDED_RNA_ADENOSINE_DEAMINASE_ACTIVITY, GOMF_TRNA_SPECIFIC_ADENOSINE_DEAMINASE_ACTIVITY, GOMF_CATALYTIC_ACTIVITY_ACTING_ON_RNA, GOMF_CATALYTIC_ACTIVITY_ACTING_ON_A_TRNA

GO Biological Process (5): adenosine to inosine editing (GO:0006382), RNA processing (GO:0006396), spermatid development (GO:0007286), spermatogenesis (GO:0007283), cell differentiation (GO:0030154)

GO Molecular Function (5): double-stranded RNA binding (GO:0003725), double-stranded RNA adenosine deaminase activity (GO:0003726), tRNA-specific adenosine deaminase activity (GO:0008251), RNA binding (GO:0003723), adenosine deaminase activity (GO:0004000)

GO Cellular Component (3): nucleus (GO:0005634), nucleolus (GO:0005730), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
deaminase activity	2
base conversion or substitution editing	1
gene expression	1
RNA biosynthetic process	1
primary metabolic process	1
germ cell development	1
spermatid differentiation	1
developmental process involved in reproduction	1
male gamete generation	1
cellular developmental process	1
RNA binding	1
adenosine deaminase activity	1
catalytic activity, acting on a tRNA	1
nucleic acid binding	1
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in cyclic amidines	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

564 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADAD2	SHOC1	Q5VXU9	583
ADAD2	M1AP	Q8TC57	516
ADAD2	RAD21L1	Q9H4I0	512
ADAD2	FBLL1	A6NHQ2	510
ADAD2	ADAT3	Q96EY9	501
ADAD2	MEIOB	Q8N635	482
ADAD2	CBY3	A6NI87	478
ADAD2	HENMT1	Q5T8I9	474
ADAD2	TEX38	Q6PEX7	472
ADAD2	TERB1	Q8NA31	472
ADAD2	NSUN7	Q8NE18	458
ADAD2	ADAT2	Q7Z6V5	456
ADAD2	TRMT10B	Q6PF06	433
ADAD2	DDX4	Q9NQI0	416
ADAD2	TRMT10C	Q7L0Y3	410

IntAct

3 interactions, top by confidence:

A	B	Type	Score
ADAD2	CRTAP	psi-mi:“MI:0914”(association)	0.350
ADAD2	TUSC2	psi-mi:“MI:0914”(association)	0.350

BioGRID (9): P3H1 (Affinity Capture-MS), TUBB8 (Affinity Capture-MS), CRTAP (Affinity Capture-MS), HSPA8 (Affinity Capture-MS), HSPA2 (Affinity Capture-MS), BAG5 (Affinity Capture-MS), TUSC2 (Affinity Capture-MS), ADAD2 (Affinity Capture-MS), APP (Reconstituted Complex)

ESM2 similar proteins: A0JNQ6, A6NC42, A6NGQ2, A6NGR9, A6QP75, A7E3N7, A9X185, E1BDF2, E9PGG2, F6SZT2, P0C7A0, P85965, Q06VW1, Q0ZFW8, Q14DK4, Q3UK37, Q3UV16, Q3ZBN4, Q400G9, Q4VXA5, Q587J8, Q5JSQ8, Q60953, Q60I26, Q60I27, Q6NUI2, Q6ZUX3, Q810I0, Q8BH06, Q8C0R7, Q8IWB1, Q8IWY9, Q8IYX4, Q8K4C2, Q8N6L0, Q8N7F7, Q8NCV1, Q8TE82, Q91WA6, Q95JV3

Diamond homologs: F4HU58, P51400, P55266, P97616, Q8NCV1, Q91ZS8, Q95JV3, Q99MU3, Q9JI20, Q9NII1, Q9NS39, A2RFW8, A8AWC2, B5XKB7, B8GAM6, C0MCR4, P0DF14, P0DF15, P55265, P66670, P66672, P78563, P97473, Q08E27, Q0IIG6, Q12906, Q15633, Q1J7V3, Q1JCZ9, Q1JI19, Q1JMX4, Q22618, Q3KR54, Q3SWU0, Q48UR6, Q5BJ52, Q5R6Y5, Q5SUE7, Q5XDA6, Q5ZIL4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	8
Likely pathogenic	1
Uncertain significance	176
Likely benign	16
Benign	1

Top pathogenic / likely-pathogenic (9)

Variant ID	HGVS	Classification
1244228	NM_001145400.2(ADAD2):c.515_516insA (p.Leu173fs)	Pathogenic
144332	GRCh38/hg38 16q22.1-24.1(chr16:70414573-84908120)x1	Pathogenic
144447	GRCh38/hg38 16q23.3-24.1(chr16:83399060-84908120)x1	Pathogenic
3063401	GRCh37/hg19 16q23.3-24.1(chr16:84009532-84245489)x1	Pathogenic
57422	GRCh38/hg38 16q23.3-24.2(chr16:83878992-87223838)x1	Pathogenic
59517	GRCh38/hg38 16q23.1-24.2(chr16:78704275-87819342)x1	Pathogenic
59518	GRCh38/hg38 16q23.3-24.1(chr16:81753762-85714791)x1	Pathogenic
59519	GRCh38/hg38 16q23.3-24.1(chr16:83016872-85087809)x1	Pathogenic
219038	GRCh37/hg19 16q23.3-24.1(chr16:83553094-86098013)x1	Likely pathogenic

SpliceAI

1754 predictions. Top by Δscore:

Variant	Effect	Δscore
16:84191275:G:GT	donor_gain	1.0000
16:84191648:GGTGA:G	donor_loss	1.0000
16:84191649:GT:G	donor_loss	1.0000
16:84191650:T:A	donor_loss	1.0000
16:84194579:CCAGG:C	donor_loss	1.0000
16:84194580:CAGGT:C	donor_loss	1.0000
16:84194581:AGGT:A	donor_loss	1.0000
16:84194582:GG:G	donor_loss	1.0000
16:84194583:GTA:G	donor_loss	1.0000
16:84194584:T:A	donor_loss	1.0000
16:84195190:GAGGG:G	donor_gain	1.0000
16:84195192:GGG:G	donor_gain	1.0000
16:84195193:GGG:G	donor_gain	1.0000
16:84195446:GGTGA:G	donor_loss	1.0000
16:84195447:GTGAG:G	donor_loss	1.0000
16:84195448:T:A	donor_loss	1.0000
16:84195678:G:GT	donor_gain	1.0000
16:84195693:ATCTA:A	donor_gain	1.0000
16:84195697:AG:A	donor_loss	1.0000
16:84195698:G:GG	donor_gain	1.0000
16:84195699:T:G	donor_loss	1.0000
16:84195802:ACCC:A	acceptor_gain	1.0000
16:84195805:C:CA	acceptor_gain	1.0000
16:84195813:A:AG	acceptor_gain	1.0000
16:84195814:G:GG	acceptor_gain	1.0000
16:84195814:GCCT:G	acceptor_gain	1.0000
16:84196043:GG:G	donor_gain	1.0000
16:84196044:GG:G	donor_gain	1.0000
16:84196045:G:GG	donor_gain	1.0000
16:84196045:G:T	donor_loss	1.0000

AlphaMissense

3701 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:84196032:A:C	S424R	0.992
16:84196034:C:A	S424R	0.992
16:84196034:C:G	S424R	0.992
16:84195657:T:G	Y338D	0.991
16:84196036:T:C	L425P	0.990
16:84195951:A:C	S397R	0.989
16:84195953:T:A	S397R	0.989
16:84195953:T:G	S397R	0.989
16:84196300:A:C	S486R	0.988
16:84196302:C:A	S486R	0.988
16:84196302:C:G	S486R	0.988
16:84196308:C:A	N488K	0.988
16:84196308:C:G	N488K	0.988
16:84195344:C:A	A261D	0.986
16:84195531:T:C	F296L	0.986
16:84195533:C:A	F296L	0.986
16:84195533:C:G	F296L	0.986
16:84196312:A:C	S490R	0.986
16:84196314:C:A	S490R	0.986
16:84196314:C:G	S490R	0.986
16:84196680:G:C	K520N	0.985
16:84196680:G:T	K520N	0.985
16:84195343:G:C	A261P	0.984
16:84195981:G:T	G407W	0.983
16:84196309:T:A	W489R	0.983
16:84196309:T:C	W489R	0.983
16:84195428:C:A	A289D	0.982
16:84195651:C:G	H336D	0.982
16:84196767:G:C	K549N	0.982
16:84196767:G:T	K549N	0.982

dbSNP variants (sampled 300 via entrez): RS1000083586 (16:84195526 C>T), RS1000288950 (16:84191961 A>C,G,T), RS1000536905 (16:84195228 G>A,C,T), RS1000635755 (16:84191394 A>T), RS1000659075 (16:84192094 C>T), RS1000909557 (16:84195072 A>G), RS1001090103 (16:84194835 G>C), RS1001607309 (16:84195472 G>A), RS1001636936 (16:84195310 A>G), RS1001799514 (16:84191754 A>G,T), RS1002154270 (16:84194732 G>A), RS1002465747 (16:84196520 A>G), RS1002608782 (16:84194797 G>A,T), RS1002643910 (16:84193139 T>C), RS1002748304 (16:84191018 C>A,G,T)

Disease associations

OMIM: gene MIM:619532 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001523_23	Visceral adipose tissue adjusted for BMI	6.000000e-06
GCST004097_3	Response to platinum-based neoadjuvant chemotherapy in cervical cancer	3.000000e-06
GCST004746_48	Small cell lung carcinoma	1.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0007943	response to platinum-based neoadjuvant chemotherapy

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, decreases methylation	1
abrine	increases expression	1
Grape Seed Proanthocyanidins	increases expression, affects cotreatment	1
Fulvestrant	affects cotreatment, decreases methylation	1
Benzo(a)pyrene	decreases methylation	1
Catechin	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

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