TLDC2

protein-coding

TBC/LysM-associated domain containing 2, the group of TLDc domain containing

Gene summary

Predicted to be involved in response to oxidative stress. Predicted to act upstream of or within negative regulation of cellular response to oxidative stress. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

C20orf118

MANE transcript

NM_080628.3

Inheritance

—

ClinVar variants

U:29B:7

Top phenotype

Aicardi-Goutieres syndrome 5

gnomAD constraint

pLI —, LoF o/e 0.39

Max pathogenic AF

—

Genomic locus

chr20:36,876,121-36,894,235

External References & Databases

Ensembl (ENSG00000101342)

Transcript & Mutation Effects

hg38 • Region Span ~18.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TLDC2 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 30

Aicardi-Goutieres syndrome 5Total: 16

Chilblain lupus 2Total: 16

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_080628.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar			1
missense			26 clinvar	5 clinvar	1 clinvar	32
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar		1 clinvar	3
Total	0	0	29	5	2	36

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 25 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_080628.3	RefSeq	NP_542195.1	6	MANE Select
ENST00000217320.8	Ensembl	ENSP00000217320.3	6	MANE Select
NM_001304783.1	RefSeq	NP_001291712.1	5	Standard
ENST00000436941.1	Ensembl	ENSP00000394804.1	2	Standard

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000217320
Coding exons: 6
Length: 18115
Individuals with no LoFs: 125719
Homozygous LoFs: 0
Heterozygous LoFs: 29
Defined: 125748
p: 0.000115

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.297	142	132	1.07	0.00000803	1395
Missense (PolyPhen)		49	47.843	1.0242		568
Synonymous	0.214	52	54.0	0.963	0.00000340	425
Loss of Function	2.01	5	12.7	0.393	6.30e-7	130

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00017	0.00017	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00014	0.00012	rare
South Asian	0.00016	0.00016	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Intolerance Scores

RVIS EVS: 0.48
RVIS percentile EVS: 79.25

Essentials

Essential (CRISPR): N
Essential (CRISPR2): E
Essential (gene trap): N

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium