CCL3L1

Chr 17

C-C motif chemokine ligand 3 like 1

Also known as: 464.2, D17S1718, G0S19-2, LD78, LD78-beta(1-70), LD78BETA, MIP1AP, SCYA3L

This gene is one of several cytokine genes that are clustered on the q-arm of chromosome 17. Cytokines are a family of secreted proteins that function in inflammatory and immunoregulatory processes. The protein encoded by this gene binds to several chemokine receptors, including chemokine binding protein 2 and chemokine (C-C motif) receptor 5 (CCR5). CCR5 is a co-receptor for HIV, and binding of this protein to CCR5 inhibits HIV entry. The copy number of this gene varies among individuals, where most individuals have one to six copies, and a minority of individuals have zero or more than six copies. There are conflicting reports about copy number variation of this gene and its correlation to disease susceptibility. This record represents one of two copies that are present on the ALT_REF_LOCI_2 alternate haplotype of the GRCh38 human reference genome assembly. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Apr 2014]

Primary Disease Associations & Inheritance

{HIV/AIDS, susceptibility to}MIM #609423

Active trials

Pathogenic / LP

ClinVar variants

Pubs (1 yr)

0.3

Missense Z

1.82

LOEUF

Clinical Summary— CCL3L1

⚡

Population Constraint (gnomAD)

Low constraint (pLI 0.12) — loss-of-function variants are relatively tolerated in the population.

📋

ClinVar Variants

24 Pathogenic / Likely Pathogenic· 9 VUS of 34 total submissions

Some data sources returned errors (1)

ensembl: Error: Ensembl fetch failed: 400 for https://rest.ensembl.org/lookup/symbol/homo_sapiens/CCL3L1?content-type=application/json&expand=1

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.

1.82LOEUF

pLI 0.121

Z-score 0.42

OE 0.64 (0.20–1.82)

Tolerant

Highly tolerant — LoF variants common in population

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.

0.27Z-score

OE missense 0.82 (0.54–1.27)

14 obs / 17.2 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.0.64 (0.20–1.82)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.82 (0.54–1.27)

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.1.03

0≤1.21.6

LoF obs/exp: 1 / 1.6Missense obs/exp: 14 / 17.2Syn Z: -0.07