Shwachman-Diamond syndrome 2

Summary

Shwachman-Diamond syndrome 2 (MONDO:0044205) is a disease caused by EFL1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: EFL1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 29

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Shwachman-Diamond syndrome 2
Mondo ID	MONDO:0044205
OMIM	617941
UMLS	C4693704
MedGen	1634617
GARD	0016272
Is cancer (heuristic)	no

Also known as: EFL1-related Shwachman-Diamond syndrome · SDS2 · Shwachman-Diamond syndrome 2

Data availability: 29 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › Shwachman-Diamond syndrome › Shwachman-Diamond syndrome 2

Related subtypes (2): Shwachman-Diamond syndrome 1, DNAJC21-related Shwachman Diamond syndrome

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

29 retrieved; paginated sample, class counts are floors:

15 uncertain significance, 4 benign, 4 likely pathogenic, 3 conflicting classifications of pathogenicity, 2 pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1686816	NM_024580.6(EFL1):c.2647T>G (p.Cys883Gly)	EFL1	Pathogenic	no assertion criteria provided
1686818	NM_024580.6(EFL1):c.2478dup (p.Gly827fs)	EFL1	Pathogenic	no assertion criteria provided
1686814	NM_024580.6(EFL1):c.2260C>T (p.Arg754Ter)	EFL1	Likely pathogenic	criteria provided, single submitter
1686815	NM_024580.6(EFL1):c.1514T>C (p.Phe505Ser)	EFL1	Likely pathogenic	criteria provided, single submitter
1686819	NM_024580.6(EFL1):c.89A>G (p.His30Arg)	EFL1	Likely pathogenic	criteria provided, single submitter
4819861	NM_024580.6(EFL1):c.1612-2A>G	EFL1	Likely pathogenic	criteria provided, single submitter
1686817	NM_024580.6(EFL1):c.3205A>G (p.Thr1069Ala)	EFL1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
522584	NM_024580.6(EFL1):c.3284G>A (p.Arg1095Gln)	EFL1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
522819	NM_024580.6(EFL1):c.379A>G (p.Thr127Ala)	EFL1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1028316	NM_024580.6(EFL1):c.2866C>A (p.Pro956Thr)	EFL1	Uncertain significance	criteria provided, single submitter
1031379	NM_024580.6(EFL1):c.1492G>A (p.Glu498Lys)	EFL1	Uncertain significance	criteria provided, single submitter
1031380	NM_024580.6(EFL1):c.2224A>G (p.Ile742Val)	EFL1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1391164	NM_024580.6(EFL1):c.1345C>T (p.His449Tyr)	EFL1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1424546	NM_024580.6(EFL1):c.787C>G (p.Leu263Val)	EFL1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2238105	NM_024580.6(EFL1):c.2548G>A (p.Gly850Ser)	EFL1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2444213	NM_024580.6(EFL1):c.3271A>C (p.Met1091Leu)	EFL1	Uncertain significance	criteria provided, single submitter
2577886	NM_024580.6(EFL1):c.2632C>A (p.Leu878Ile)	EFL1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3377765	NM_024580.6(EFL1):c.2371A>G (p.Met791Val)	EFL1	Uncertain significance	criteria provided, single submitter
3602646	NM_024580.6(EFL1):c.67dup (p.Cys23fs)	EFL1	Uncertain significance	criteria provided, single submitter
4819867	NM_024580.6(EFL1):c.1750+7693G>A	EFL1	Uncertain significance	criteria provided, single submitter
522583	NM_024580.6(EFL1):c.2645T>A (p.Met882Lys)	EFL1	Uncertain significance	criteria provided, single submitter
636244	NM_024580.6(EFL1):c.1232T>A (p.Ile411Asn)	EFL1	Uncertain significance	criteria provided, multiple submitters, no conflicts
636245	NM_024580.6(EFL1):c.1971C>G (p.His657Gln)	EFL1	Uncertain significance	criteria provided, single submitter
985047	NM_024580.6(EFL1):c.2908C>T (p.Arg970Cys)	EFL1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1165404	NM_024580.6(EFL1):c.2358T>C (p.Gly786=)	EFL1	Benign	criteria provided, multiple submitters, no conflicts
1167286	NM_024580.6(EFL1):c.1434G>C (p.Glu478Asp)	EFL1	Benign	criteria provided, multiple submitters, no conflicts
1255374	NM_024580.6(EFL1):c.2990-36T>C	EFL1	Benign	criteria provided, multiple submitters, no conflicts
1255375	NM_024580.6(EFL1):c.731+18T>C	EFL1	Benign	criteria provided, multiple submitters, no conflicts
1592337	NM_024580.6(EFL1):c.1398A>G (p.Gln466=)	EFL1	Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
EFL1	Strong	Autosomal recessive	Shwachman-Diamond syndrome 2	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
EFL1	Orphanet:811	Shwachman-Diamond syndrome

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
EFL1	HGNC:25789	ENSG00000140598	Q7Z2Z2	Elongation factor-like GTPase 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
EFL1	Elongation factor-like GTPase 1	GTPase involved in the biogenesis of the 60S ribosomal subunit and translational activation of ribosomes.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
EFL1	Enzyme (other)	yes	3.6.5.3	EFG_V-like, T_Tr_GTP-bd_dom, Small_GTP-bd

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
oocyte	1
secondary oocyte	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
EFL1	241	ubiquitous	marker	secondary oocyte, oocyte, ventricular zone

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
EFL1	4,645

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
EFL1	Q7Z2Z2	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
cytosolic ribosome assembly	1	2407.4×	8e-04	EFL1
GTP metabolic process	1	1123.5×	9e-04	EFL1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
EFL1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
EFL1	3.6.5.3	protein-synthesizing GTPase

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	EFL1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
EFL1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.