ANXA11

Summary

ANXA11 (annexin A11, HGNC:535) is a protein-coding gene on chromosome 10q22.3, encoding Annexin A11 (P50995). Binds specifically to calcyclin in a calcium-dependent manner.

This gene encodes a member of the annexin family, a group of calcium-dependent phospholipid-binding proteins. Annexins have unique N-terminal domains and conserved C-terminal domains, which contain calcium-dependent phospholipid-binding sites. The encoded protein is a 56-kD antigen recognized by sera from patients with various autoimmune diseases. Several transcript variants encoding two different isoforms have been identified.

Source: NCBI Gene 311 — RefSeq curated summary.

At a glance

• Gene–disease (curated): amyotrophic lateral sclerosis type 23 (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 5
• Clinical variants (ClinVar): 487 total — 8 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 71
• Druggable target: yes
• MANE Select transcript: NM_145868

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:535
Approved symbol	ANXA11
Name	annexin A11
Location	10q22.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000122359
Ensembl biotype	protein_coding
OMIM	602572
Entrez	311

Gene structure

Transcript identifiers

Ensembl transcripts: 63 — 59 protein_coding, 3 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000265447, ENST00000372231, ENST00000422982, ENST00000437799, ENST00000438331, ENST00000447489, ENST00000463340, ENST00000463657, ENST00000474545, ENST00000481805, ENST00000856386, ENST00000856387, ENST00000856388, ENST00000856389, ENST00000856390, ENST00000856391, ENST00000856392, ENST00000856393, ENST00000856394, ENST00000856395, ENST00000856396, ENST00000856397, ENST00000856398, ENST00000856399, ENST00000856400, ENST00000856401, ENST00000856402, ENST00000856403, ENST00000856404, ENST00000856405, ENST00000856406, ENST00000856407, ENST00000856408, ENST00000856409, ENST00000856410, ENST00000856411, ENST00000856412, ENST00000856413, ENST00000856414, ENST00000856415, ENST00000918175, ENST00000918176, ENST00000963276, ENST00000963277, ENST00000963278, ENST00000963279, ENST00000963280, ENST00000963281, ENST00000963282, ENST00000963283, ENST00000963284, ENST00000963285, ENST00000963286, ENST00000963287, ENST00000963288, ENST00000963289, ENST00000963290, ENST00000963291, ENST00000963292, ENST00000963293, ENST00000963294, ENST00000963295, ENST00000963296

RefSeq mRNA: 6 — MANE Select: NM_145868 NM_001157, NM_001278407, NM_001278408, NM_001278409, NM_145868, NM_145869

CCDS: CCDS60576, CCDS7364

Canonical transcript exons

ENST00000422982 — 16 exons

Exon	Start	End
ENSE00000909276	80157641	80157763
ENSE00000909277	80157967	80158025
ENSE00000909278	80159100	80159195
ENSE00000909279	80161935	80162028
ENSE00001376996	80176107	80176155
ENSE00001457270	80150889	80155912
ENSE00002448092	80164053	80164143
ENSE00002460881	80163534	80163613
ENSE00002494992	80166084	80166197
ENSE00002509632	80166890	80166984
ENSE00002518768	80168969	80169358
ENSE00002521933	80163349	80163405
ENSE00003531093	80172807	80172869
ENSE00003585307	80167226	80167313
ENSE00003646683	80170800	80170915
ENSE00003848771	80205343	80205537

Expression profiles

Bgee: expression breadth ubiquitous, 300 present calls, max score 99.47.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 159.3642 / max 1740.3528, expressed in 1827 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
110337	110.3877	1826
110338	44.7742	1825
110330	1.7990	1086
110331	0.5920	332
110328	0.5853	337
110339	0.4039	195
110323	0.3904	182
110329	0.2959	113
110340	0.0969	31
110333	0.0245	10

Top tissues by expression

301 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	99.47	gold quality
palpebral conjunctiva	UBERON:0001812	99.24	gold quality
mucosa of transverse colon	UBERON:0004991	99.19	gold quality
apex of heart	UBERON:0002098	99.17	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.11	gold quality
esophagus mucosa	UBERON:0002469	99.05	gold quality
colonic epithelium	UBERON:0000397	99.00	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.00	gold quality
esophagus squamous epithelium	UBERON:0006920	98.98	gold quality
right atrium auricular region	UBERON:0006631	98.96	gold quality
metanephros cortex	UBERON:0010533	98.91	gold quality
granulocyte	CL:0000094	98.90	gold quality
epithelium of esophagus	UBERON:0001976	98.89	gold quality
blood	UBERON:0000178	98.81	gold quality
heart left ventricle	UBERON:0002084	98.81	gold quality
cardiac ventricle	UBERON:0002082	98.78	gold quality
bronchial epithelial cell	CL:0002328	98.73	gold quality
ascending aorta	UBERON:0001496	98.72	gold quality
thoracic aorta	UBERON:0001515	98.71	gold quality
esophagus	UBERON:0001043	98.66	gold quality
epithelium of bronchus	UBERON:0002031	98.62	gold quality
upper lobe of left lung	UBERON:0008952	98.58	gold quality
descending thoracic aorta	UBERON:0002345	98.56	gold quality
bronchus	UBERON:0002185	98.55	gold quality
body of stomach	UBERON:0001161	98.54	gold quality
right coronary artery	UBERON:0001625	98.54	gold quality
oral cavity	UBERON:0000167	98.53	gold quality
cardiac atrium	UBERON:0002081	98.52	gold quality
heart	UBERON:0000948	98.51	gold quality
aorta	UBERON:0000947	98.50	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-81547	yes	23.71
E-HCAD-10	yes	23.16
E-MTAB-7606	no	659.02
E-GEOD-75367	no	550.25
E-MTAB-6386	no	407.14
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

56 targeting ANXA11, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-7156-5P	99.64	68.81	1369
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-4524A-5P	99.57	71.73	1193
HSA-MIR-4524B-5P	99.57	71.68	1195
HSA-MIR-6832-3P	99.52	70.44	1726
HSA-MIR-6833-5P	99.50	68.93	1161
HSA-MIR-3128	99.50	67.85	1258
HSA-MIR-147B-5P	99.45	70.62	2432

Literature-anchored findings (GeneRIF, showing 40)

• Body patterning of legs is a product of this gene. (PMID:15680373)
• Data show that Aristaless and Clawless proteins form a complex capable of binding to specific DNA targets, which cannot be well recognized solely by Aristaless or Clawless. (PMID:15733670)
• Mutational analysis shows that the number of Smad- and Zen-binding sites is essential for the C15 transcriptional response, and the spatial limits of C15 expression are established through a repression mechanism in the dorsolateral cells of the embryo. (PMID:17092951)
• In the Al-Cll-DNA complex structure, the residues in the extended regions are used not only for the intermolecular contacts between the two homeodomain proteins but also for the sequence-recognition mechanism of DNA by direct interactions. (PMID:20389279)
• we find that C15 interacts physically with the Dll activator through contacts between their homeodomain and binds competitively with Dll to adjacent cognate sites on LAE, adding potential new layers of regulation by C15. Lastly, we show that C15 and Bowl activities regulate also rn expression (PMID:28394894)
• Pro/Gly/Tyr/Ala-rich hydrophobic region in AnxN masked the Ca(2+)-dependently exposed hydrophobic surface of ALG-2. (PMID:11883939)
• The penta-EF-hand domain of ALG-2 interacts with the amino-terminal domain of annexin XI in a Ca2+-dependent manner. (PMID:12445460)
• calcium- and cell cycle-dependent association with the nuclear envelope (PMID:12601007)
• annexin XI associates with the mitotic spindles and might play a role in cell division (PMID:12805373)
• Annexin 11-depleted cells failed to complete cytokinesis and died by apoptosis, demonstrating an essential role for annexin 11. (PMID:15197175)
• The strongest association signal maps to the ANXA11 (annexin A11) gene on chromosome 10q22.3. (PMID:19165924)
• These findings indicate that the polymorphisms of ANXA6 are associated with osteonecrosis of the femoral head. (PMID:19345290)
• Immunohistochemistry analyses indicated that annexin A11 immunointensity inversely correlated with HMOX1 immunoreactivity in 142 ovarian cancer patients. (PMID:19484149)
• analysis of the sarcoidosis-associated variant of annexin A11 (PMID:20093723)
• A7 and A11 have sequence repeats that form novel structures, called YP pro-beta helices, that are characterized by an ability to interact with one another (PMID:20093729)
• Data confirm the strong association between variations in ANXA11 and sarcoidosis and support the hypothesis that ANXA11 represents a strong genetic risk factor for sarcoidosis. (PMID:20805159)
• ANXA11 rs1049550 single nucleotide polymorphism is the susceptibility marker in sarcoidosis, at least in Caucasians. (PMID:21562576)
• ANXA11 SNPs are associated with sarcoidosis in African Americans. (PMID:23151485)
• LIFR rs3729740 and possibly ANXA11 rs1049550 may be useful as biomarkers for predicting whether metastatic colorectal cancer patients are sensitive to relevant target regimens, although further validation in large cohorts is needed. (PMID:23579219)
• Annexin A11 rs1049550*T allele exerts a significant protective effect on sarcoidosis susceptibility. (PMID:24032725)
• the associations of Anxa11 with Ca(2+)-regulated exocytosis, cytokinesis, sex differentiation, autoimmune diseases, thrombolysis and cancers are summarized–{REVIEW} (PMID:24508622)
• These findings point to a role for the polymorphisms of ANXA11 in sarcoidosis in a Chinese Han population, and may be informative for future genetic studies on sarcoidosis. (PMID:25056970)
• findings suggest that AnxA11 maintains architectural and functional features of the ERES by coordinating with ALG-2 to stabilize Sec31A at the ERES. (PMID:25540196)
• ANXA11 rs1049550 and PPP1R15A rs557806 may improve the identification of mCRC patients sensitive to bevacizumab regimens, and further validation is required in large cohorts (PMID:27177629)
• Review/Meta-analysis: ANXA11 SNP rs2573346 and rs2789679 conferred protection against sarcoidosis. SNP rs1049550 may be a risk factor for sarcoidosis in overall population. (PMID:27537711)
• Letter: ANXA11 SNPs increase susceptibility to fibrosing sarcoiodosis in African Americans. (PMID:28079857)
• Data conclude that mutations in ANXA11 are associated with ALS and implicate defective intracellular protein trafficking in disease pathogenesis. (PMID:28469040)
• ANXA11 plays a critical role in regulating gastric cancer proliferation, migration, and invasion. (PMID:29306955)
• Genetic variants in RAB23 and ANXA11 genes were associated with an increased risk of sarcoidosis-associated uveitis. (PMID:29416296)
• Pathogenic ANXA11 mutations are absent or rare in ALS patients in Taiwan. (PMID:30054183)
• Both ANXA11 G38R protein and ANXA11 D40G protein showed a shorter half-life than ANXA11 wild type protein, while there was no difference between ANXA11 G38R protein and ANXA11 D40G protein. There was no visible insoluble substance in the NP-40 lysates for ANXA11 wild type protein, ANXA11 G38R protein and ANXA11 D40G protein. G38R and D40G mutations reduce the stability of ANXA11 protein. (PMID:30109997)
• Its mutation is associated with ALS. (PMID:30337194)
• Association of TGF-beta3 and ANXA11 with pulmonary sarcoidosis in Greek population. (PMID:32552203)
• ANXA11 mutations in ALS cause dysregulation of calcium homeostasis and stress granule dynamics. (PMID:33087501)
• Genetic screening of ANXA11 revealed novel mutations linked to amyotrophic lateral sclerosis. (PMID:33218681)
• A Novel Multisystem Proteinopathy Caused by a Missense ANXA11 Variant. (PMID:34048612)
• ANXA1 with Anti-Inflammatory Properties Might Contribute to Parkinsonism. (PMID:34180078)
• Subcellular Proteome Analysis Reveals Apoptotic Vulnerability of T-Cell Acute Lymphoblastic Leukemia. (PMID:35463978)
• ANXA11 rs1049550 Associates with Lofgren’s Syndrome and Chronic Sarcoidosis Patients. (PMID:35563867)
• CircSOD2 Contributes to Tumor Progression, Immune Evasion and Anti-PD-1 Resistance in Hepatocellular Carcinoma by Targeting miR-497-5p/ANXA11 Axis. (PMID:36008700)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	anxa11b	ENSDARG00000002632
danio_rerio	anxa11a	ENSDARG00000077383
mus_musculus	Anxa11	ENSMUSG00000021866
rattus_norvegicus	Anxa11	ENSRNOG00000010984
drosophila_melanogaster	AnxB9	FBGN0000083
drosophila_melanogaster	AnxB11	FBGN0030749

Paralogs (12): ANXA13 (ENSG00000104537), ANXA10 (ENSG00000109511), ANXA1 (ENSG00000135046), ANXA7 (ENSG00000138279), ANXA3 (ENSG00000138772), ANXA9 (ENSG00000143412), ANXA5 (ENSG00000164111), ANXA2 (ENSG00000182718), ANXA4 (ENSG00000196975), ANXA6 (ENSG00000197043), ANXA8L1 (ENSG00000264230), ANXA8 (ENSG00000265190)

Protein

Protein identifiers

Annexin A11 — P50995 (reviewed: P50995)

Alternative names: 56 kDa autoantigen, Annexin XI, Annexin-11, Calcyclin-associated annexin 50

All UniProt accessions (4): P50995, H0Y6E1, Q5T0G7, Q5T0G8

UniProt curated annotations — full annotation on UniProt →

Function. Binds specifically to calcyclin in a calcium-dependent manner. Required for midbody formation and completion of the terminal phase of cytokinesis.

Subunit / interactions. Interacts with S100A6. Interacts with PDCD6 in a calcium-dependent manner. Interacts with KIF23 during cytokinesis.

Subcellular location. Cytoplasm. Melanosome. Nucleus envelope. Nucleus. Nucleoplasm. Cytoskeleton. Spindle.

Disease relevance. Amyotrophic lateral sclerosis 23 (ALS23) [MIM:617839] A form of amyotrophic lateral sclerosis, a neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases. ALS23 is an autosomal dominant form with incomplete penetrance. The disease is caused by variants affecting the gene represented in this entry. Inclusion body myopathy and brain white matter abnormalities (IBMWMA) [MIM:619733] An autosomal dominant, adult-onset disorder characterized predominantly by proximal limb girdle muscle weakness affecting the lower and upper limbs and resulting in gait difficulties and scapular winging. Additional features may include dysarthria, dysphagia, low back pain, and hyporeflexia. Muscle biopsy shows fiber type variation, internal nuclei, rimmed vacuoles, and cytoplasmic protein aggregates or inclusions. Cognitive impairment or frontotemporal dementia occurs in some patients. The gene represented in this entry is involved in disease pathogenesis.

Domain organisation. A pair of annexin repeats may form one binding site for calcium and phospholipid.

Similarity. Belongs to the annexin family.

Isoforms (2)

UniProt ID	Names	Canonical?
P50995-1	1	yes
P50995-2	2

RefSeq proteins (6): NP_001148, NP_001265336, NP_001265337, NP_001265338, NP_665875, NP_665876 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001464	Annexin	Family
IPR008157	ANX11	Family
IPR018252	Annexin_repeat_CS	Conserved_site
IPR018502	Annexin_repeat	Repeat
IPR037104	Annexin_sf	Homologous_superfamily

Pfam: PF00191

UniProt features (26 total): sequence variant 10, repeat 4, modified residue 3, compositionally biased region 3, strand 2, region of interest 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
9FOR	ELECTRON MICROSCOPY	2.75
9FOF	ELECTRON MICROSCOPY	2.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P50995-F1	77.32	0.63

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (3): 248, 255, 479

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 348 (showing top): GOCC_SECRETORY_GRANULE, DITTMER_PTHLH_TARGETS_UP, HSIAO_HOUSEKEEPING_GENES, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, GOBP_VESICLE_MEDIATED_TRANSPORT, CHANDRAN_METASTASIS_DN, GOBP_CYTOKINETIC_PROCESS, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, GOBP_RESPONSE_TO_METAL_ION, GTGCCTT_MIR506, ONKEN_UVEAL_MELANOMA_UP, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, GOBP_CYTOKINESIS, AAAGGGA_MIR204_MIR211, GOTZMANN_EPITHELIAL_TO_MESENCHYMAL_TRANSITION_DN

GO Biological Process (4): phagocytosis (GO:0006909), cytokinetic process (GO:0032506), response to calcium ion (GO:0051592), cell division (GO:0051301)

GO Molecular Function (9): phosphatidylserine binding (GO:0001786), RNA binding (GO:0003723), calcium ion binding (GO:0005509), calcium-dependent phospholipid binding (GO:0005544), phosphatidylethanolamine binding (GO:0008429), MHC class II protein complex binding (GO:0023026), S100 protein binding (GO:0044548), calcium-dependent protein binding (GO:0048306), protein binding (GO:0005515)

GO Cellular Component (17): nucleus (GO:0005634), nuclear envelope (GO:0005635), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), spindle (GO:0005819), cytosol (GO:0005829), plasma membrane (GO:0005886), vesicle membrane (GO:0012506), membrane (GO:0016020), midbody (GO:0030496), extracellular matrix (GO:0031012), melanosome (GO:0042470), specific granule (GO:0042581), azurophil granule (GO:0042582), phagocytic vesicle (GO:0045335), extracellular exosome (GO:0070062), cytoskeleton (GO:0005856)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
phospholipid binding	3
protein binding	2
intracellular membraneless organelle	2
secretory granule	2
endocytosis	1
cytokinesis	1
cell cycle process	1
response to metal ion	1
cellular process	1
anion binding	1
modified amino acid binding	1
nucleic acid binding	1
metal ion binding	1
MHC protein complex binding	1
calcium ion binding	1
binding	1
intracellular membrane-bounded organelle	1
nucleus	1
endomembrane system	1
organelle envelope	1
nuclear lumen	1
intracellular anatomical structure	1
microtubule cytoskeleton	1
cytoplasm	1
membrane	1
cell periphery	1
organelle membrane	1
vesicle	1
external encapsulating structure	1
pigment granule	1
primary lysosome	1
endocytic vesicle	1
extracellular vesicle	1

Protein interactions and networks

STRING

1116 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ANXA11	S100A6	P06703	978
ANXA11	BTNL2	Q9UIR0	841
ANXA11	HSPA1L	P34931	635
ANXA11	PEF1	Q9UBV8	603
ANXA11	SEC31A	O94979	597
ANXA11	HLA-DRB1	P01911	571
ANXA11	PLAA	Q9Y263	552
ANXA11	CST4	P01036	551
ANXA11	SLC11A1	P49279	537
ANXA11	TSG101	Q99816	515
ANXA11	CALM1	P02593	494
ANXA11	HSPA4	P34932	487
ANXA11	CALML4	Q96GE6	486
ANXA11	CALML3	P27482	478
ANXA11	PDCD6	O75340	475

IntAct

83 interactions, top by confidence:

A	B	Type	Score
NRAS	RAF1	psi-mi:“MI:0914”(association)	0.930
ANXA11	CEP55	psi-mi:“MI:0915”(physical association)	0.780
CEP55	ANXA11	psi-mi:“MI:0915”(physical association)	0.780
ANXA11	PDCD6	psi-mi:“MI:0915”(physical association)	0.750
PDCD6	ANXA11	psi-mi:“MI:0915”(physical association)	0.750
ANXA11	TFG	psi-mi:“MI:0915”(physical association)	0.670
TFG	ANXA11	psi-mi:“MI:0915”(physical association)	0.670
ANXA11	FUBP1	psi-mi:“MI:0915”(physical association)	0.560
ANXA11	KRTAP6-2	psi-mi:“MI:0915”(physical association)	0.560
ANXA11	WWOX	psi-mi:“MI:0915”(physical association)	0.560
ANXA11	KRTAP13-2	psi-mi:“MI:0915”(physical association)	0.560
ARSA	ANXA11	psi-mi:“MI:0915”(physical association)	0.560
ANXA11	NFKBID	psi-mi:“MI:0915”(physical association)	0.560
PLSCR1	ANXA11	psi-mi:“MI:0915”(physical association)	0.550
ANXA11	PLSCR1	psi-mi:“MI:0915”(physical association)	0.550
CD81	C2orf72	psi-mi:“MI:0914”(association)	0.530
ANXA11	E6	psi-mi:“MI:0915”(physical association)	0.490
	AP3D1	psi-mi:“MI:0914”(association)	0.460

BioGRID (145): PDCD6 (Two-hybrid), TFG (Two-hybrid), CEP55 (Two-hybrid), ANXA11 (Two-hybrid), ANXA11 (Affinity Capture-MS), PLSCR1 (Two-hybrid), ANXA11 (Co-fractionation), ANXA11 (Co-fractionation), ANXA11 (Co-fractionation), ANXA11 (Co-fractionation), ANXA11 (Co-fractionation), ANXA11 (Co-fractionation), ANXA2 (Co-fractionation), ASS1 (Co-fractionation), C11orf54 (Co-fractionation)

ESM2 similar proteins: A1CL82, A1CQZ0, A1CXK7, A1D3V4, A1D611, A2QI25, A2QU58, A2RB75, A3LSY7, A4QTY2, A5D9W7, A5DZS4, A6R7B8, A6SDT7, A6SEH9, A6ZP43, A7EJY3, A7F075, B0XPP3, B0Y081, O74477, P08699, P0CM58, P0CM59, P16110, P17931, P20072, P27214, P30601, P33477, P47953, P50995, P97384, Q08601, Q0CQL9, Q0CTN3, Q1E0A3, Q2UCB7, Q2UN81, Q4PEQ5

Diamond homologs: A2SW69, A5A6L7, A5A6M2, A6NMY6, C0HJG9, C1L7Y4, C4QH88, O35639, O35640, O76027, O97529, P04083, P04272, P07150, P07355, P07356, P08132, P08133, P08758, P09525, P10107, P12429, P13214, P13928, P14087, P14668, P14669, P14824, P14950, P17153, P17785, P19619, P19620, P20072, P20073, P22464, P22465, P24551, P24639, P24801

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

487 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	8
Likely pathogenic	1
Uncertain significance	268
Likely benign	116
Benign	65

Top pathogenic / likely-pathogenic (9)

Variant ID	HGVS	Classification
146022	GRCh38/hg38 10q22.3-23.2(chr10:79925613-86951708)x1	Pathogenic
2444454	NM_145868.2(ANXA11):c.118_119delinsAT (p.Asp40Ile)	Pathogenic
3244818	NC_000010.10:g.(?81697608)(82049179_?)del	Pathogenic
3393203	NM_145868.2(ANXA11):c.744+1G>A	Pathogenic
395199	GRCh37/hg19 10q22.3-23.2(chr10:81892411-88722952)x1	Pathogenic
488353	NM_145868.2(ANXA11):c.119A>G (p.Asp40Gly)	Pathogenic
58754	GRCh38/hg38 10q22.3-23.2(chr10:79898516-86964367)x1	Pathogenic
981172	Single allele	Pathogenic
4083415	NM_145868.2(ANXA11):c.119A>T (p.Asp40Val)	Likely pathogenic

SpliceAI

2710 predictions. Top by Δscore:

Variant	Effect	Δscore
10:80155800:T:TA	donor_gain	1.0000
10:80157759:GCCCC:G	acceptor_gain	1.0000
10:80157760:CCCC:C	acceptor_gain	1.0000
10:80157760:CCCCC:C	acceptor_gain	1.0000
10:80157761:CCC:C	acceptor_gain	1.0000
10:80157761:CCCC:C	acceptor_gain	1.0000
10:80157762:CC:C	acceptor_gain	1.0000
10:80157762:CCC:C	acceptor_gain	1.0000
10:80157763:CC:C	acceptor_gain	1.0000
10:80157764:C:CC	acceptor_gain	1.0000
10:80157965:AC:A	donor_gain	1.0000
10:80157966:CC:C	donor_gain	1.0000
10:80158021:TTTCA:T	acceptor_gain	1.0000
10:80158024:CA:C	acceptor_gain	1.0000
10:80158026:C:CC	acceptor_gain	1.0000
10:80159191:GAAAA:G	acceptor_gain	1.0000
10:80159192:AAAA:A	acceptor_gain	1.0000
10:80159193:AAA:A	acceptor_gain	1.0000
10:80159194:AA:A	acceptor_gain	1.0000
10:80159195:AC:A	acceptor_loss	1.0000
10:80159196:C:CC	acceptor_gain	1.0000
10:80159198:A:AC	acceptor_gain	1.0000
10:80159198:A:C	acceptor_gain	1.0000
10:80161930:CTTAC:C	donor_loss	1.0000
10:80161932:TAC:T	donor_loss	1.0000
10:80161933:A:AC	donor_gain	1.0000
10:80161933:ACCT:A	donor_loss	1.0000
10:80161934:C:A	donor_loss	1.0000
10:80161934:C:CC	donor_gain	1.0000
10:80162025:GCTCC:G	acceptor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000003603 (10:80205611 G>A), RS1000005841 (10:80201984 C>G,T), RS1000093545 (10:80168909 T>C), RS1000139360 (10:80188029 G>A,T), RS1000214679 (10:80187734 C>T), RS1000239694 (10:80186468 C>T), RS1000254926 (10:80161578 T>C), RS1000292035 (10:80150858 G>C), RS1000477108 (10:80193831 CAG>C), RS1000523909 (10:80178412 T>A,C), RS1000597165 (10:80151941 G>A), RS1000667026 (10:80150461 C>G), RS1000676873 (10:80186294 G>A), RS1000705095 (10:80172855 A>G), RS1000769651 (10:80174204 C>A,T)

Disease associations

OMIM: gene MIM:602572 | disease phenotypes: MIM:619733, MIM:617839, MIM:164300, MIM:250850

GenCC curated gene-disease

Disease	Classification	Inheritance
amyotrophic lateral sclerosis type 23	Definitive	Autosomal dominant
inclusion body myopathy and brain white matter abnormalities	Moderate	Autosomal dominant
amyotrophic lateral sclerosis	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
amyotrophic lateral sclerosis type 23	Definitive	AD

Mondo (6): inclusion body myopathy and brain white matter abnormalities (MONDO:0850514), amyotrophic lateral sclerosis (MONDO:0004976), amyotrophic lateral sclerosis type 23 (MONDO:0027694), oculopharyngeal muscular dystrophy 1 (MONDO:0958176), methionine adenosyltransferase deficiency (MONDO:0009607), neurodevelopmental disorder (MONDO:0700092)

Orphanet (2): Amyotrophic lateral sclerosis (Orphanet:803), Methionine adenosyltransferase I/III deficiency (Orphanet:168598)

HPO phenotypes

71 total (30 of 71 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000217	Xerostomia
HP:0000508	Ptosis
HP:0000708	Atypical behavior
HP:0000712	Emotional lability
HP:0000716	Depression
HP:0000726	Dementia
HP:0000739	Anxiety
HP:0001257	Spasticity
HP:0001260	Dysarthria
HP:0001265	Hyporeflexia
HP:0001284	Areflexia
HP:0001308	Tongue fasciculations
HP:0001347	Hyperreflexia
HP:0001618	Dysphonia
HP:0001824	Weight loss
HP:0002015	Dysphagia
HP:0002094	Dyspnea
HP:0002145	Frontotemporal dementia
HP:0002180	Neurodegeneration
HP:0002307	Drooling
HP:0002313	Spastic paraparesis
HP:0002360	Sleep disturbance
HP:0002380	Fasciculations
HP:0002398	Degeneration of anterior horn cells
HP:0002463	Language impairment
HP:0002878	Respiratory failure
HP:0003202	Skeletal muscle atrophy
HP:0003236	Elevated circulating creatine kinase concentration
HP:0003324	Generalized muscle weakness

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST001654_2	Sarcoidosis	1.000000e-06
GCST001737_9	Chronic obstructive pulmonary disease-related biomarkers	1.000000e-10
GCST003098_8	Diabetic kidney disease	9.000000e-07
GCST005542_5	Sarcoidosis (non-Lofgren’s syndrome without extrapulmonary manifestations)	4.000000e-06
GCST011437_4	Sarcoidosis	1.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005081	surfactant protein D measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D000690	Amyotrophic Lateral Sclerosis	C10.228.854.139; C10.574.562.250; C10.574.950.050; C10.668.467.250; C18.452.845.800.050
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066274 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1049550	ANXA11		0.00	0

CTD chemical–gene interactions

67 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	7
bisphenol A	decreases expression, decreases methylation, affects cotreatment, increases expression	4
Tretinoin	increases expression	3
Cadmium Chloride	decreases reaction, increases abundance, increases palmitoylation, increases expression	3
bisphenol F	increases expression, affects cotreatment, decreases expression	2
sodium arsenite	increases abundance, decreases expression, affects cotreatment	2
cobaltous chloride	decreases expression	2
Nickel	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tetrachlorodibenzodioxin	increases expression	2
dicrotophos	increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	decreases expression	1
decabromobiphenyl ether	decreases expression	1
trichostatin A	increases expression	1
butyraldehyde	decreases expression	1
2-bromopalmitate	increases abundance, increases palmitoylation, decreases reaction	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
4-aminophenylarsenoxide	decreases reaction, affects binding	1
isobutyl alcohol	decreases expression, increases abundance, affects cotreatment	1
epigallocatechin gallate	decreases expression	1
pentanal	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
JP8 aviation fuel	affects expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
bisphenol B	increases expression	1
2-amino-14,16-dimethyloctadecan-3-ol	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5650896	Binding	Binding affinity to human ANXA11 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

13 cell lines: 10 induced pluripotent stem cell, 2 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A5RB	KCLi011-A	Induced pluripotent stem cell	Male
CVCL_A5RC	KCLi012-A	Induced pluripotent stem cell	Female
CVCL_A5RD	KCLi013-A	Induced pluripotent stem cell	Female
CVCL_B2RQ	Abcam HEK293T ANXA11 KO	Transformed cell line	Female
CVCL_B3SH	HeLa ANXA11 KO	Cancer cell line	Female
CVCL_C7ZV	HAP1 ANXA11 (-)	Cancer cell line	Male
CVCL_E4NQ	KOLF2.1J ANXA11 17.0kbdel DEL/DEL	Induced pluripotent stem cell	Male
CVCL_E4NS	KOLF2.1J ANXA11 D40G SNV/SNV	Induced pluripotent stem cell	Male
CVCL_E4NT	KOLF2.1J ANXA11 D40G SNV/WT	Induced pluripotent stem cell	Male
CVCL_E4NV	KOLF2.1J ANXA11 G38R SNV/SNV	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00542412	PHASE4	COMPLETED	CARE Canadian ALS Riluzole Evaluation
NCT00560287	PHASE4	UNKNOWN	Non-Invasive Ventilation in Amyotrophic Lateral Sclerosis
NCT00613899	PHASE4	COMPLETED	Feasibility of Telesurveillance and Home Cough Assistance for Amyotrophic Lateral Patients (ALS)
NCT04997954	PHASE4	UNKNOWN	EMERALD TRIAL Open Label Extension Study
NCT06849115	PHASE4	COMPLETED	Effects of L-Carnitine in Amyotrophic Lateral Sclerosis Patients With CHCHD10 Mutations
NCT07223723	PHASE4	RECRUITING	A Study to Learn More About the Long-Term Safety of Tofersen (Qalsody) in Chinese Participants With SOD-1 Amyotrophic Lateral Sclerosis (ALS)
NCT00021697	PHASE3	COMPLETED	Safety/Efficacy of AVP-923 in the Treatment of Emotional Lability (Uncontrolled Crying & Laughing) in Patients With ALS
NCT00035815	PHASE3	COMPLETED	Insulin-like Growth Factor-1 in Amyotrophic Lateral Sclerosis (ALS) Trial
NCT00047723	PHASE3	COMPLETED	Minocycline to Treat Amyotrophic Lateral Sclerosis
NCT00069186	PHASE3	UNKNOWN	Study of Creatine Monohydrate in Patients With Amyotrophic Lateral Sclerosis
NCT00136110	PHASE3	COMPLETED	Trial of Sodium Valproate in Amyotrophic Lateral Sclerosis
NCT00330681	PHASE3	COMPLETED	Efficacy and Safety Study of MCI-186 for Treatment of Amyotrophic Lateral Sclerosis (ALS)
NCT00349622	PHASE3	COMPLETED	Clinical Trial Ceftriaxone in Subjects With ALS
NCT00372879	PHASE3	COMPLETED	Clinical Trial of Vitamin E to Treat Muscular Cramps in Patients With ALS
NCT00415519	PHASE3	COMPLETED	Efficacy and Safety Study of MCI-186 for Treatment of Amyotrophic Lateral Sclerosis (ALS) Who Met Severity Classification III
NCT00424463	PHASE3	COMPLETED	Expanded Controlled Study of Safety and Efficacy of MCI-186 in Patients With Amyotrophic Lateral Sclerosis (ALS)
NCT00839033	PHASE3	TERMINATED	Evaluation of a Mechanical Device During Acute Respiratory Failure in Patients With Neuromuscular Disorders
NCT00868166	PHASE3	COMPLETED	Safety and Efficacy of TRO19622 as add-on Therapy to Riluzole Versus Placebo in Treatment of Patients Suffering From ALS
NCT00965497	PHASE3	COMPLETED	Escitalopram (Lexapro) for Depression MS or ALS
NCT01016522	PHASE3	TERMINATED	Safety and Tolerability of the Ketogenic Diet in Amyotrophic Lateral Sclerosis (ALS)
NCT01160263	PHASE3	COMPLETED	Study of Dopamine and Serotonin Transporters in Patients With Amyotrophic Lateral Sclerosis and Controls
NCT01281189	PHASE3	COMPLETED	Phase 3 Study of Dexpramipexole in ALS
NCT01492686	PHASE3	COMPLETED	Phase 3 Study of MCI-186 for Treatment of Amyotrophic Lateral Sclerosis
NCT01583088	PHASE3	TERMINATED	Early Stage Amyotrophic Lateral Sclerosis Phrenic Stimulation
NCT01622088	PHASE3	TERMINATED	Phase 3 Extension Study of Dexpramipexole in ALS
NCT02496767	PHASE3	COMPLETED	Ventilatory Investigation of Tirasemtiv and Assessment of Longitudinal Indices After Treatment for a Year
NCT02623699	PHASE3	COMPLETED	An Efficacy, Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of BIIB067 (Tofersen) in Adults With Inherited Amyotrophic Lateral Sclerosis (ALS)
NCT02936635	PHASE3	COMPLETED	A Study for Patients Who Completed VITALITY-ALS (CY 4031)
NCT03127267	PHASE3	RECRUITING	Efficacy and Safety of Masitinib Versus Placebo in the Treatment of ALS Patients
NCT03280056	PHASE3	COMPLETED	Safety and Efficacy of Repeated Administrations of NurOwn® in ALS Patients
NCT03491462	PHASE3	COMPLETED	Arimoclomol in Amyotropic Lateral Sclerosis
NCT03505021	PHASE3	COMPLETED	Effects of Oral Levosimendan (ODM-109) on Respiratory Function in Patients With ALS
NCT03548311	PHASE3	COMPLETED	Clinical Trial of Ultra-high Dose Methylcobalamin for ALS
NCT03690791	PHASE3	UNKNOWN	Efficacy of Cannabinoids in Amyotrophic Lateral Sclerosis or Motor Neurone Disease
NCT03800524	PHASE3	UNKNOWN	Safety and Efficacy of TUDCA as add-on Treatment in Patients Affected by ALS
NCT03836716	PHASE3	TERMINATED	Arimoclomol in Amyotropic Lateral Sclerosis - Open Label Extension Trial
NCT03948178	PHASE3	TERMINATED	Effects of Oral Levosimendan on Respiratory Function in Patients With Amyotrophic Lateral Sclerosis (ALS): Open-Label Extension
NCT04165824	PHASE3	COMPLETED	Safety Study of Oral Edaravone Administered in Subjects With ALS
NCT04248465	PHASE3	TERMINATED	An Efficacy and Safety Study of Ravulizumab in ALS Participants
NCT04569084	PHASE3	TERMINATED	Efficacy and Safety Study of Oral Edaravone Administered in Subjects With ALS