DLEC1

Chr 3

DLEC1 cilia and flagella associated protein

Also known as: CFAP81, DLC-1, DLC1, F56, FAP81

NCBI Gene: 9940 ENSG00000008226 UniProt: Q9Y238

The protein encoded by DLEC1 is essential for spermatogenesis and may function as a tumor suppressor by inhibiting cell proliferation. The gene is not highly constrained against loss-of-function variants and clinical phenotypes associated with germline mutations in pediatric patients are not well-established in current databases. DLEC1 is primarily known for its down-regulation in various adult malignancies rather than monogenic pediatric neurological disorders.

ResearchSummary from RefSeq, UniProt

The cytogenetic location of this gene is 3p21.3, and it is located in a region that is commonly deleted in a variety of malignancies. Down-regulation of this gene has been observed in several human cancers including lung, esophageal, renal tumors, and head and neck squamous cell carcinoma. In some cases, reduced expression of this gene in tumor cells is a result of aberrant promoter methylation. Several alternatively spliced transcripts have been observed that contain disrupted coding regions and likely encode nonfunctional proteins.[provided by RefSeq, Mar 2016]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtLung cancer

UniProtEsophageal cancer

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.91

LOEUF

—

Mechanism

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.91LOEUF

pLI 0.000

Z-score 2.26

OE 0.74 (0.61–0.91)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.50Z-score

OE missense 1.04 (0.99–1.10)

1044 obs / 999.6 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.74 (0.61–0.91)

0≤0.351.4

Missense OE?1.04 (0.99–1.10)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 67 / 90.1Missense obs/exp: 1044 / 999.6Syn Z: -0.66

Background carrier burden — how many people carry a rare variant somewhere in DLEC1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 17

2,501 rare PASS variants

Rare truncating (LoF)

1 in 220

394 rare PASS variants

Rare synonymous (reference)

1 in 42

982 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for DLEC1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 26	1 in 270
South Asian	~43k	1 in 18	1 in 220
Remaining (unassigned)	~30k	1 in 17	1 in 160
European (Finnish)	~27k	1 in 91	1 in 290
Admixed American	~22k	1 in 18	1 in 200
African / African American	~21k	1 in 19	1 in 120
East Asian	~20k	1 in 21	1 in 300
Ashkenazi Jewish	~13k	1 in 90	1 in 340
Middle Eastern	~2,884	1 in 18	1 in 220

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 37 coding exons well covered in gnomAD exomes and genomes.? see exons ↓