SAMD9L

Chr 7AD

sterile alpha motif domain containing 9 like

Also known as: ATXPC, C7DELq, C7orf6, DEL7q, DRIF2, M7MLS1, MLSM7, SCA49

NCBI Gene: 219285 ENSG00000177409 UniProt: Q8IVG5

This gene encodes a cytoplasmic protein that acts as a tumor suppressor but also plays a key role in cell proliferation and the innate immune response to viral infection. The encoded protein contains an N-terminal sterile alpha motif domain. Naturally occurring mutations in this gene are associated with myeloid disorders such as juvenile myelomonocytic leukemia, acute myeloid leukemia, and myelodysplastic syndrome. Naturally occurring mutations are also associated with hepatitis-B related hepatocellular carcinoma, normophosphatemic familial tumoral calcinosis, and ataxia-pancytopenia syndrome. [provided by RefSeq, Apr 2017]

Primary Disease Associations & Inheritance

?Spinocerebellar ataxia 49MIM #619806

Ataxia-pancytopenia syndromeMIM #159550

Monosomy 7 myelodysplasia and leukemia syndrome 1MIM #252270

695

ClinVar variants

Pathogenic / LP

0.00

pLI score

Active trials

Clinical Summary— SAMD9L

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Gene-Disease Validity (ClinGen)

SAMD9L-related spectrum and myeloid neoplasm risk · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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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 Pathogenic / Likely Pathogenic· 472 VUS of 695 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Some data sources returned errors (1)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.

0.78LOEUF

pLI 0.000

Z-score 2.86

OE 0.58 (0.44–0.78)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.

1.63Z-score

OE missense 0.84 (0.78–0.89)

661 obs / 790.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.

LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.58 (0.44–0.78)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.84 (0.78–0.89)

0≤0.61.4

Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.04

0≤1.21.6

LoF obs/exp: 32 / 54.9Missense obs/exp: 661 / 790.3Syn Z: -0.51