CRYL1

Chr 13

crystallin lambda 1

Also known as: GDH, HEL30, gul3DH, lambda-CRY

NCBI Gene: 51084 ENSG00000165475 UniProt: Q9Y2S2

The protein catalyzes the conversion of L-gulonate to 3-dehydro-L-gulonate in the uronate cycle, an alternative glucose metabolic pathway. Mutations cause autosomal recessive nonsyndromic deafness, typically presenting in childhood. CRYL1 has a GeneReviews entry reflecting its established clinical significance in hereditary hearing loss.

GeneReviews ResearchSummary from RefSeq, UniProt

The uronate cycle functions as an alternative glucose metabolic pathway, accounting for about 5% of daily glucose catabolism. The product of this gene catalyzes the dehydrogenation of L-gulonate into dehydro-L-gulonate in the uronate cycle. The enzyme requires NAD(H) as a coenzyme, and is inhibited by inorganic phosphate. A similar gene in the rabbit is thought to serve a structural role in the lens of the eye. [provided by RefSeq, Jul 2008]

GeneReviews ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.06

LOEUF

Multiple*

Mechanism· predicted

📖

GeneReview available — CRYL1

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

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?

1.06LOEUF

pLI 0.000

Z-score 1.37

OE 0.64 (0.40–1.06)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.40Z-score

OE missense 0.92 (0.81–1.04)

169 obs / 184.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.64 (0.40–1.06)

0≤0.351.4

Missense OE?0.92 (0.81–1.04)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 11 / 17.1Missense obs/exp: 169 / 184.4Syn Z: 0.44

Background carrier burden — how many people carry a rare variant somewhere in CRYL1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 150

434 rare PASS variants

Rare truncating (LoF)

1 in 840

90 rare PASS variants

Rare synonymous (reference)

1 in 160

169 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CRYL1. 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 230	1 in 870
South Asian	~43k	1 in 110	1 in 360
Remaining (unassigned)	~30k	1 in 110	1 in 260
European (Finnish)	~27k	1 in 1,000	1 in 5,300
Admixed American	~22k	1 in 180	1 in 2,200
African / African American	~21k	1 in 69	1 in 790
East Asian	~20k	1 in 110	1 in 380
Ashkenazi Jewish	~13k	1 in 570	none seen
Middle Eastern	~2,884	1 in 130	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): 7 of 8 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 8.? see exons ↓