LMAN1

Chr 18AR

lectin, mannose binding 1

Also known as: ERGIC-53, ERGIC53, F5F8D, FMFD1, MCFD1, MR60, gp58

The encoded protein is a mannose-specific lectin that functions as a cargo receptor for glycoprotein transport between the endoplasmic reticulum and Golgi apparatus. Mutations cause combined factor V and VIII deficiency, an autosomal recessive bleeding disorder. The gene is not highly constrained (low pLI), consistent with recessive inheritance where heterozygous carriers are typically unaffected.

Summary from RefSeq, OMIM, UniProt
Research Assistant →

Primary Disease Associations & Inheritance

Combined factor V and VIII deficiencyMIM #227300
AR
UniProtFactor V and factor VIII combined deficiency 1
0
Active trials
8
Pubs (1 yr)
89
P/LP submissions
1%
P/LP missense
0.55
LOEUF
DN
Mechanism· predicted
Clinical SummaryLMAN1
🧬
Gene-Disease Validity (ClinGen)
factor V and factor VIII, combined deficiency of, type 1 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.32) despite low pLI — interpret in context.
📋
ClinVar Variants
85 unique Pathogenic / Likely Pathogenic· 153 VUS of 312 total submissions
📖
GeneReview available — LMAN1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.55LOEUF
pLI 0.004
Z-score 3.50
OE 0.32 (0.200.55)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.06Z-score
OE missense 0.99 (0.901.09)
270 obs / 272.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.32 (0.200.55)
00.351.4
Missense OE0.99 (0.901.09)
00.61.4
Synonymous OE1.05
01.21.6
LoF obs/exp: 10 / 31.1Missense obs/exp: 270 / 272.9Syn Z: -0.38
DN
0.7034th %ile
GOF
0.5856th %ile
LOF
0.3162th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

312 submitted variants in ClinVar

Classification Summary

Pathogenic77
Likely Pathogenic8
VUS153
Likely Benign16
Benign45
Conflicting5
77
Pathogenic
8
Likely Pathogenic
153
VUS
16
Likely Benign
45
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
1
71
0
77
Likely Pathogenic
3
0
4
1
8
VUS
0
92
56
5
153
Likely Benign
0
7
8
1
16
Benign
0
3
37
5
45
Conflicting
5
Total810317612304

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

LMAN1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC