SCGB1D1

Chr 11

secretoglobin family 1D member 1

Also known as: LIPA, LPHA, LPNA

NCBI Gene: 10648 ENSG00000168515 UniProt: O95968 OMIM: 615060

The protein encoded by SCGB1D1 is a secretory glycoprotein that binds androgens and other steroids and is a component of a heterodimeric molecule present in human tears. This gene is not highly constrained against loss-of-function variants and no definitive disease associations have been established in the provided data. The protein may be transcriptionally regulated by steroid hormones and can potentially bind chemotherapeutic agents like estramustine.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is a member of the lipophilin subfamily, part of the uteroglobin superfamily, and is an ortholog of prostatein, the major secretory glycoprotein of the rat ventral prostate gland. This gene product represents one component of a heterodimeric molecule present in human tears whose elution profile is consistent with prostatein, a tetrameric molecule composed of three peptide components in heterodimers. Assuming that human lipophilins are the functional counterparts of prostatein, they may be transcriptionally regulated by steroid hormones, with the ability to bind androgens, other steroids and possibly bind and concentrate estramustine, a chemotherapeutic agent widely used for prostate cancer. Although the gene has been reported to be on chromosome 15, this sequence appears to be from a cluster of genes on chromosome 11 that includes mammaglobin 2. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.97

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.97LOEUF

pLI 0.000

Z-score -2.15

OE 2.22 (1.04–1.97)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.14Z-score

OE missense 1.06 (0.84–1.33)

51 obs / 48.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?2.22 (1.04–1.97)

0≤0.351.4

Missense OE?1.06 (0.84–1.33)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 8 / 3.6Missense obs/exp: 51 / 48.3Syn Z: 0.06

Background carrier burden — how many people carry a rare variant somewhere in SCGB1D1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 250

106 rare PASS variants

Rare truncating (LoF)

1 in 1,400

18 rare PASS variants

Rare synonymous (reference)

1 in 1,400

51 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SCGB1D1. 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 360	1 in 1,300
South Asian	~43k	1 in 190	1 in 1,600
Remaining (unassigned)	~30k	1 in 290	1 in 890
European (Finnish)	~27k	1 in 570	≈ 1 in 27,000
Admixed American	~22k	1 in 330	1 in 3,700
African / African American	~21k	1 in 280	≈ 1 in 8,400
East Asian	~20k	1 in 530	1 in 4,000
Ashkenazi Jewish	~13k	≈ 1 in 6,500	1 in 690
Middle Eastern	~2,884	1 in 210	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 3 coding exons well covered in gnomAD exomes and genomes.? see exons ↓