ADAD2

Chr 16

adenosine deaminase domain containing 2

Also known as: TENRL

NCBI Gene: 161931 ENSG00000140955 UniProt: Q8NCV1 OMIM: 619532

The protein functions as a double-stranded RNA adenosine deaminase that performs adenosine to inosine editing during RNA processing and is required for male fertility and normal male germ cell differentiation. Based on the extremely low pLI score (2.39e-12) and LOEUF score above 1 (1.144), this gene appears highly tolerant to loss-of-function mutations. No specific diseases associated with ADAD2 mutations have been established in the provided clinical data.

OMIM ResearchSummary from RefSeq, UniProt

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. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOEUF 1.14

Clinical Summary— ADAD2

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 162 VUS of 186 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.14LOEUF

pLI 0.000

Z-score 0.98

OE 0.79 (0.56–1.14)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-2.36Z-score

OE missense 1.32 (1.24–1.42)

553 obs / 417.4 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.79 (0.56–1.14)

0≤0.351.4

Missense OE?1.32 (1.24–1.42)

0≤0.61.4

Synonymous OE?1.50

0≤1.21.6

LoF obs/exp: 21 / 26.4Missense obs/exp: 553 / 417.4Syn Z: -5.47

ClinVar Variant Classifications

186 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

VUS162

Likely Benign16

Pathogenic

162

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Synonymous	Total
Pathogenic	1	0	0	1
Likely Pathogenic	0	0	0	0
VUS	0	162	0	162
Likely Benign	0	13	3	16
Benign	0	0	0	0
Total	1	175	3	179

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

45 pathogenic / likely-pathogenic (of 73) ClinVar copy-number / structural variants overlap ADAD2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →