Amyotrophic lateral sclerosis type 23

disease

On this page

Also known as ALS23

Summary

Amyotrophic lateral sclerosis type 23 (MONDO:0027694) is a disease caused by ANXA11 (GenCC Definitive), with 1 cohort gene.

At a glance

Causal gene: ANXA11 (GenCC Definitive)
Cohort genes: 1
ClinVar variants: 19

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	amyotrophic lateral sclerosis type 23
Mondo ID	MONDO:0027694
OMIM	617839
DOID	DOID:0080225
UMLS	C4693381
MedGen	1645924
GARD	0016262
Is cancer (heuristic)	no

Also known as: ALS23

Data availability: 19 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › spinal cord disorder › anterior horn disorder › amyotrophic lateral sclerosis › familial amyotrophic lateral sclerosis › amyotrophic lateral sclerosis type 23

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

19 retrieved; paginated sample, class counts are floors:

11 uncertain significance, 2 benign/likely benign, 2 pathogenic, 2 pathogenic/likely pathogenic, 1 likely benign, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
3393203	NM_145868.2(ANXA11):c.744+1G>A	ANXA11	Pathogenic	criteria provided, single submitter
488353	NM_145868.2(ANXA11):c.119A>G (p.Asp40Gly)	ANXA11	Pathogenic	criteria provided, single submitter
488354	NM_145868.2(ANXA11):c.112G>A (p.Gly38Arg)	ANXA11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
802593	NM_145868.2(ANXA11):c.118G>T (p.Asp40Tyr)	ANXA11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1607012	NM_145868.2(ANXA11):c.905G>A (p.Arg302His)	ANXA11	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1398399	NM_145868.2(ANXA11):c.1424G>A (p.Arg475Gln)	ANXA11	Uncertain significance	criteria provided, single submitter
1447044	NM_145868.2(ANXA11):c.1010_1011delinsAA (p.Leu337Gln)	ANXA11	Uncertain significance	criteria provided, multiple submitters, no conflicts
1706565	NM_145868.2(ANXA11):c.607del (p.Leu203fs)	ANXA11	Uncertain significance	no assertion criteria provided
1711861	NM_145868.2(ANXA11):c.904C>T (p.Arg302Cys)	ANXA11	Uncertain significance	criteria provided, multiple submitters, no conflicts
1943820	NM_145868.2(ANXA11):c.744+2C>T	ANXA11	Uncertain significance	criteria provided, multiple submitters, no conflicts
1966979	NM_145868.2(ANXA11):c.1382G>A (p.Arg461His)	ANXA11	Uncertain significance	criteria provided, multiple submitters, no conflicts
2634560	NM_145868.2(ANXA11):c.438_461del (p.Thr151_Val158del)	ANXA11	Uncertain significance	criteria provided, multiple submitters, no conflicts
3779545	NM_145868.2(ANXA11):c.1010T>A (p.Leu337His)	ANXA11	Uncertain significance	criteria provided, single submitter
4531569	NM_145868.2(ANXA11):c.223C>T (p.Pro75Ser)	ANXA11	Uncertain significance	criteria provided, single submitter
4819859	NM_145868.2(ANXA11):c.834T>G (p.Ile278Met)	ANXA11	Uncertain significance	criteria provided, single submitter
488355	NM_145868.2(ANXA11):c.523G>A (p.Gly175Arg)	ANXA11	Uncertain significance	criteria provided, single submitter
1499369	NM_145868.2(ANXA11):c.654G>A (p.Thr218=)	ANXA11	Likely benign	criteria provided, single submitter
1624615	NM_145868.2(ANXA11):c.962C>A (p.Thr321Asn)	ANXA11	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
1646325	NM_145868.2(ANXA11):c.322C>T (p.Pro108Ser)	ANXA11	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · 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
ANXA11	Definitive	Autosomal dominant	amyotrophic lateral sclerosis type 23	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ANXA11	Orphanet:803	Amyotrophic lateral sclerosis

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
ANXA11	HGNC:535	ENSG00000122359	P50995	Annexin A11	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ANXA11	Annexin A11	Binds specifically to calcyclin in a calcium-dependent manner.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ANXA11	Other/Unknown	no		Annexin, ANX11, Annexin_repeat_CS

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
lower esophagus mucosa	1
mucosa of transverse colon	1
palpebral conjunctiva	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ANXA11	300	ubiquitous	marker	lower esophagus mucosa, palpebral conjunctiva, mucosa of transverse colon

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ANXA11	1,344

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ANXA11	P50995	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
cytokinetic process	1	5617.3×	5e-04	ANXA11
response to calcium ion	1	318.0×	0.004	ANXA11
phagocytosis	1	240.7×	0.004	ANXA11

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ANXA11	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
ANXA11	7	Binding:7

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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	ANXA11

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)
ANXA11	7	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: ANXA11