MMACHC

Summary

MMACHC (metabolism of cobalamin associated C, HGNC:24525) is a protein-coding gene on chromosome 1p34.1, encoding Cyanocobalamin reductase / alkylcobalamin dealkylase (Q9Y4U1). Cobalamin (vitamin B12) cytosolic chaperone that catalyzes the reductive decyanation of cyanocob(III)alamin (cyanocobalamin, CNCbl) to yield cob(II)alamin and cyanide, using FAD or FMN as cofactors and NADPH as cosubstrate.

The exact function of the protein encoded by this gene is not known, however, its C-terminal region shows similarity to TonB, a bacterial protein involved in energy transduction for cobalamin (vitamin B12) uptake. Hence, it is postulated that this protein may have a role in the binding and intracellular trafficking of cobalamin. Mutations in this gene are associated with methylmalonic aciduria and homocystinuria type cblC.

Source: NCBI Gene 25974 — RefSeq curated summary.

At a glance

• Gene–disease (curated): methylmalonic aciduria and homocystinuria type cblC (Definitive, ClinGen)
• GWAS associations: 16
• Clinical variants (ClinVar): 694 total — 58 pathogenic, 49 likely-pathogenic
• Phenotypes (HPO): 113
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_015506

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24525
Approved symbol	MMACHC
Name	metabolism of cobalamin associated C
Location	1p34.1
Locus type	gene with protein product
Status	Approved
Aliases	DKFZP564I122, cblC
Ensembl gene	ENSG00000132763
Ensembl biotype	protein_coding
OMIM	609831
Entrez	25974

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000401061, ENST00000477188, ENST00000616135, ENST00000933807

RefSeq mRNA: 2 — MANE Select: NM_015506 NM_001330540, NM_015506

CCDS: CCDS41324, CCDS81315

Canonical transcript exons

ENST00000401061 — 4 exons

Exon	Start	End
ENSE00000905999	45507356	45507550
ENSE00001141158	45508212	45508364
ENSE00001456871	45500300	45500413
ENSE00001546178	45508796	45513382

Expression profiles

Bgee: expression breadth ubiquitous, 177 present calls, max score 82.39.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.1811 / max 92.3771, expressed in 1712 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
2688	14.3338	1702
2687	0.6861	391
2689	0.1612	63

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	82.39	gold quality
liver	UBERON:0002107	81.42	gold quality
hindlimb stylopod muscle	UBERON:0004252	77.73	gold quality
stromal cell of endometrium	CL:0002255	77.52	gold quality
ventricular zone	UBERON:0003053	77.11	gold quality
mucosa of transverse colon	UBERON:0004991	77.11	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.80	gold quality
right atrium auricular region	UBERON:0006631	76.46	gold quality
heart left ventricle	UBERON:0002084	75.83	gold quality
cardiac ventricle	UBERON:0002082	75.52	gold quality
cardiac atrium	UBERON:0002081	75.49	gold quality
prefrontal cortex	UBERON:0000451	75.22	gold quality
heart	UBERON:0000948	74.05	gold quality
muscle of leg	UBERON:0001383	73.89	gold quality
right adrenal gland	UBERON:0001233	73.81	gold quality
apex of heart	UBERON:0002098	73.67	gold quality
gastrocnemius	UBERON:0001388	73.25	gold quality
right adrenal gland cortex	UBERON:0035827	72.96	gold quality
rectum	UBERON:0001052	72.88	gold quality
left adrenal gland	UBERON:0001234	72.58	gold quality
ganglionic eminence	UBERON:0004023	72.52	gold quality
cortical plate	UBERON:0005343	72.17	gold quality
left adrenal gland cortex	UBERON:0035825	71.95	gold quality
colonic epithelium	UBERON:0000397	71.46	gold quality
adrenal gland	UBERON:0002369	71.30	gold quality
islet of Langerhans	UBERON:0000006	71.22	gold quality
adrenal tissue	UBERON:0018303	70.89	gold quality
adult mammalian kidney	UBERON:0000082	70.87	gold quality
adrenal cortex	UBERON:0001235	70.85	gold quality
muscle organ	UBERON:0001630	70.36	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-9543	yes	34.79
E-ANND-3	yes	13.26
E-CURD-10	no	110.67
E-ENAD-17	no	87.20

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HCFC1

miRNA regulators (miRDB)

66 targeting MMACHC, 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-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-3162-3P	100.00	65.37	363
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-6512-3P	99.65	66.07	1468
HSA-MIR-6720-5P	99.65	66.22	1459
HSA-MIR-1251-3P	99.64	67.21	1408
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-1287-3P	99.63	66.93	492
HSA-MIR-6126	99.62	68.09	996
HSA-MIR-4643	99.49	67.63	1791
HSA-MIR-208A-5P	99.42	70.83	1913
HSA-MIR-208B-5P	99.42	70.83	1952
HSA-MIR-6828-5P	99.31	69.21	1433
HSA-MIR-6878-3P	99.24	64.23	920
HSA-MIR-642A-3P	99.23	67.67	1258
HSA-MIR-642B-3P	99.23	67.67	1258
HSA-MIR-6744-3P	99.22	64.41	972
HSA-MIR-3125	99.14	68.49	2269

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• One mutation, 271dupA, in MMACHC accounted for 40% of all disease alleles. (PMID:16311595)
• Mutation analysis of the MMACHC gene showed that both patients were homozygous for 394C –> T which suggests a founder effect in Late onset cobalamin C disorder. (PMID:17431913)
• c.271dupA (accounting for 55% of the MMACH alleles in our cohort) followed by c.394C>T (16%) and c.331C>T (9%) were the most frequent mutations. (PMID:18164228)
• Most patients (eight of nine patients investigated) were compound heterozygotes for the 271dupA mutation and a missense mutation. (PMID:18245139)
• MMACHC catalyzes a reductive decyanation reaction that removes the cyanide group in vitamin B(12) or cyanocobalamin (PMID:18779575)
• A new mutation (146_154 del CCTTCCTGG) in the MMACHC gene was detected in a Chinese family with methylmalonic aciduria. (PMID:19199254)
• Epigenetic inactivation of the MMACHC gene is responsible for methionine dependence in human melanoma cell line MeWo-LC1. (PMID:19200761)
• MMACHC was sequenced from the DNA of 118 cblC individuals. Eleven novel mutations were identified.Genotype-phenotype correlations of common mutations were apparent. (PMID:19370762)
• These studies suggest that the CblC protein is responsible for early processing of both CNCbl (decyanation) and alkylcobalamins (dealkylation) in mammalian cells. (PMID:19447654)
• MMACHC with the G147D mutation is unable to bind either cyanocobalamin or hydroxocobalamin, providing a straight forward explanation for the absence of response to either vitamin form. (PMID:19700356)
• Mutations in MMACHC are associated with altered cellular oxidative stress and apoptosis processes in the presence or absence of vitamin B(12). (PMID:19760748)
• Diverse and clinically significant structural heart defects appear to be highly prevalent in cblC type methylmalonic aciduria and homocystinuria. (PMID:19767224)
• Data show that the catalytic turnover numbers for the dealkylation of methylcobalamin and 5’-deoxyadenosylcobalamin by MMACHC are 11.7 +/- 0.2 and 0.174 +/- 0.006 h(-1) at 20 degrees C, respectively. (PMID:19801555)
• MMACHC-wt and MMACHC-R161Q are both very thermolabile proteins in their apo forms, with melting temperatures (T(m)) of 39.3+/-1.0 and 37.1+/-0.7 degrees C, respectively (PMID:20219402)
• defects occurring in the MMACHC gene are the major cause of this disease in Chinese patients with combined methylmalonic aciduria and homocystinuria (PMID:20631720)
• MMADHC was confirmed as a binding partner for MMACHC both in vitro (SPR) and in vivo (bacterial two-hybrid system). (PMID:21071249)
• a structural framework provides a framework for understanding catalytic function and disease mechanism for the multifunctional MMACHC complex. (PMID:22642810)
• The function of MMADHC is exerted through its structured C-terminal domain via interactions with MMACHC. (PMID:22832074)
• Subcellular location of MMACHC and MMADHC, two human proteins central to intracellular vitamin B(12) metabolism. (PMID:23270877)
• data suggest that the interaction of methionine synthase with MMACHC may play a role in the regulation of the cellular processing of cobalamins that is required for cobalamin cofactor synthesis (PMID:23825108)
• The gene responsible for cblC, named MMACHC, catalyzes the reductive decyanation of cyanocobalamin. (PMID:24577983)
• mutation analysis of the MMACHC gene in four patients revealed novel heterozygous mutations at nucleotide 276 (c.276G > A [p.Glu926Glu] and c.276G > T [p.Glu92Asp]), which is located at the end of exon 2. (PMID:24853097)
• HCFC1 plays a role in craniofacial development, which is in part mediated through the regulation of MMACHC expression (PMID:25281006)
• Results propose a model whereby membrane-bound LMBD1 and ABCD4 facilitate the vectorial delivery of lysosomal vitamin B12 to cytoplasmic MMACHC. (PMID:25535791)
• an adult patient with bull’s eye macular lesions and no clinically relevant systemic symptoms was diagnosed with cblC by genetic screening and follow-up biochemical laboratory tests. (PMID:25687216)
• Five different known mutations in either MUT or MMACHC genes were identified in seven of the eight Chinese patients with methyl malonic acidemia. (PMID:25982642)
• A novel mutation p.G155R of the MMACHC gene is identified in prenatal diagnosis of combined methylmalonic aciduria and homocystinuria. (PMID:26149271)
• MMACHC mutation was found in children diagnosed with hemolytic uremic syndrome secondary to cobalamin C disorder. (PMID:26253414)
• These results indicated that hypergonadotropic hypogonadism may be a novel clinical manifestation of cblC disease, but more reports on additional patients are needed to support this hypothesis. (PMID:26283149)
• the MMACHC-MMADHC complex is a 1:1 heterodimer, where the interaction region overlaps with the MMACHC-Cbl binding site (PMID:26483544)
• Sequencing of the MMACHC gene is used for confirming the diagnosis of cblC disease. MMACHC mutations were found in all the nine patients. 7 different mutations were identified, including c.609G>A, c.455_457delCCC, c.394C>T, c.445_446insA, c.658_660delAAG, c.452A>G and IVS1+1G>A. The most frequent mutation was c.609G>A (6/9). Two patients had homozygous mutations (c.445_446insA/c.445_446insA and c.609G>A/c.609G>A). (PMID:26563984)
• Case Report: c.567dupT,p.(Ile190Tyrfs*13) MMACHC heterozygous mutation underlying methylmalonic academia in infant. (PMID:27383490)
• These data show that the processing of cobalamin in cytoplasm occurs in a multiprotein complex composed of at least methionine synthase, methionine synthase reductase, MMACHC and MMADHC. (PMID:27771510)
• The crystal structure of ceCblC provides insights into how architectural differences at the alpha- and beta-faces of cobalamin promote the thiol oxidase activity of ceCblC but mute it in wild-type human CblC. (PMID:28442570)
• Partial CblC-type inherited Methylmalonic acidemia (MMACHC heterozygous mutation exonl: c. 80A >G, c. 609G >A) can onset with severe metabolic Atypical hemolytic uremic syndrome. (PMID:29068997)
• The epimutation is present in three generations and results from PRDX1 mutations that force antisense transcription of MMACHC. (PMID:29302025)
• THAP11F80L exhibited a strong effect on association with the MMACHC promoter and led to a decrease in MMACHC gene transcription, suggesting that the THAP11F80L mutation is directly responsible for the observed cobalamin disorder (PMID:31905202)
• Generation of a Human iPSC line (SDQLCHi021-A) from a patient with methylmalonic acidemia cblC type carrying compound heterozygous mutations in MMAHC gene. (PMID:32058304)
• Analysis of fibroblasts from patients with cblC and cblG genetic defects of cobalamin metabolism reveals global dysregulation of alternative splicing. (PMID:32068834)
• The vitamin B12 processing enzyme, mmachc, is essential for zebrafish survival, growth and retinal morphology. (PMID:32186706)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	mmachc	ENSDARG00000043877
mus_musculus	Mmachc	ENSMUSG00000028690
rattus_norvegicus	Mmachc	ENSRNOG00000017233
caenorhabditis_elegans		WBGENE00022766

Protein

Protein identifiers

Cyanocobalamin reductase / alkylcobalamin dealkylase — Q9Y4U1 (reviewed: Q9Y4U1)

Alternative names: Alkylcobalamin:glutathione S-alkyltransferase, CblC, Cyanocobalamin reductase (cyanide-eliminating), Methylmalonic aciduria and homocystinuria type C protein

All UniProt accessions (2): Q9Y4U1, A0A0C4DGU2

UniProt curated annotations — full annotation on UniProt →

Function. Cobalamin (vitamin B12) cytosolic chaperone that catalyzes the reductive decyanation of cyanocob(III)alamin (cyanocobalamin, CNCbl) to yield cob(II)alamin and cyanide, using FAD or FMN as cofactors and NADPH as cosubstrate. Cyanocobalamin constitutes the inactive form of vitamin B12 introduced from the diet, and is converted into the active cofactors methylcobalamin (MeCbl) involved in methionine biosynthesis, and 5’-deoxyadenosylcobalamin (AdoCbl) involved in the TCA cycle. Forms a complex with the lysosomal transporter ABCD4 and its chaperone LMBRD1, to transport cobalamin across the lysosomal membrane into the cytosol. The processing of cobalamin in the cytosol occurs in a multiprotein complex composed of at least MMACHC, MMADHC, MTRR (methionine synthase reductase) and MTR (methionine synthase) which may contribute to shuttle safely and efficiently cobalamin towards MTR in order to produce methionine. Also acts as a glutathione transferase by catalyzing the dealkylation of the alkylcob(III)alamins MeCbl and AdoCbl, using the thiolate of glutathione for nucleophilic displacement to generate cob(I)alamin and the corresponding glutathione thioether. The conversion of incoming MeCbl or AdoCbl into a common intermediate cob(I)alamin is necessary to meet the cellular needs for both cofactors. Cysteine and homocysteine cannot substitute for glutathione in this reaction.

Subunit / interactions. Monomer in the absence of bound substrate. Homodimer; dimerization is triggered by binding to FMN or adenosylcobalamin. Interacts with LMBRD1 and ABCD4; the interaction ensures the transport of cobalamin from the lysosome to the cytoplasm. Forms a multiprotein complex with MMADHC, MTR and MTRR; the interaction with MTR could modulate MMACHC-dependent processing of cobalamin. Heterodimer with MMADHC; the interaction might play a role in the regulation of the balance between AdoCbl and MeCbl synthesis.

Subcellular location. Cytoplasm. Cytosol.

Tissue specificity. Widely expressed. Expressed at higher level in fetal liver. Also expressed in spleen, lymph node, thymus and bone marrow. Weakly or not expressed in peripheral blood leukocytes.

Disease relevance. Methylmalonic aciduria and homocystinuria, cblC type (MAHCC) [MIM:277400] An autosomal recessive disorder of cobalamin metabolism characterized by decreased levels of the coenzymes adenosylcobalamin (AdoCbl) and methylcobalamin (MeCbl). Affected individuals may have developmental, hematologic, neurologic, metabolic, ophthalmologic, and dermatologic clinical findings. Although considered a disease of infancy or childhood, some individuals develop symptoms in adulthood. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Can utilize both FAD and FMN.

Similarity. Belongs to the MMACHC family.

RefSeq proteins (2): NP_001317469, NP_056321* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR032037	MMACHC	Family

Pfam: PF16690

Enzyme classification (BRENDA):

• EC 2.5.1.151 — alkylcobalamin dealkylase (BRENDA: 2 organisms, 20 substrates, 0 inhibitors, 0 Km, 12 kcat entries)

Substrate kinetics (BRENDA)

9 substrates with measured Km, best-characterized 9. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
5’-DEOXYADENOSYLCOBALAMIN	—	0
BUTYRYLCOBALAMIN	—	0
CYANOCOBALAMIN	—	0
ETHYLCOBALAMIN	—	0
HEXYLCOBALAMIN	—	0
METHYLCOBALAMIN	—	0
NITROCOBALAMIN	—	0
PENTYLCOBALAMIN	—	0
PROPYLCOBALAMIN	—	0

Catalyzed reactions (Rhea), 4 shown:

• 2 cob(II)alamin-[cyanocobalamin reductase] + 2 hydrogen cyanide + NADP(+) = 2 cyanocob(III)alamin + 2 apo-[cyanocobalamin reductase] + NADPH + H(+) (RHEA:16113)
• apo-[alkylcobalamin reductase] + an R-cob(III)alamin + glutathione = cob(I)alamin-[alkylcobalamin reductase] + an S-substituted glutathione + H(+) (RHEA:40719)
• apo-[alkylcobalamin reductase] + methylcob(III)alamin + glutathione = S-methyl glutathione + cob(I)alamin-[alkylcobalamin reductase] + H(+) (RHEA:63132)
• apo-[alkylcobalamin reductase] + adenosylcob(III)alamin + glutathione = S-adenosylglutathione + cob(I)alamin-[alkylcobalamin reductase] + H(+) (RHEA:63136)

UniProt features (56 total): sequence variant 15, helix 15, strand 9, binding site 5, modified residue 4, mutagenesis site 3, turn 2, chain 1, region of interest 1, sequence conflict 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
7WUZ	X-RAY DIFFRACTION	1.93
3SC0	X-RAY DIFFRACTION	1.95
3SBZ	X-RAY DIFFRACTION	2
3SOM	X-RAY DIFFRACTION	2.4
5UOS	X-RAY DIFFRACTION	2.51
3SBY	X-RAY DIFFRACTION	2.71
9MRS	X-RAY DIFFRACTION	3.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y4U1-F1	86.41	0.76

Functional residue map

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

Ligand- & substrate-binding residues (5): 104; 115–118; 129–131; 149; 160

Post-translational modifications (4): 279, 245, 247, 275

Mutagenesis-validated functional residues (3):

Position	Phenotype
122	reduced affinity for cyanocobalamin.
206	impairs protein folding.
230	reduced activity in dealkylation of methylcobalamin.

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-3359473	Defective MMADHC causes MMAHCD
R-HSA-3359474	Defective MMACHC causes MAHCC
R-HSA-9759218	Cobalamin (Cbl) metabolism
R-HSA-1430728	Metabolism
R-HSA-1643685	Disease
R-HSA-196741	Cobalamin (Cbl, vitamin B12) transport and metabolism
R-HSA-196849	Metabolism of water-soluble vitamins and cofactors
R-HSA-196854	Metabolism of vitamins and cofactors
R-HSA-3296469	Defects in cobalamin (B12) metabolism
R-HSA-3296482	Defects in vitamin and cofactor metabolism
R-HSA-5668914	Diseases of metabolism

MSigDB gene sets: 501 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_UP, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, GOBP_REGULATION_OF_ERBB_SIGNALING_PATHWAY, GOBP_NEGATIVE_REGULATION_OF_ERBB_SIGNALING_PATHWAY, ROVERSI_GLIOMA_COPY_NUMBER_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_MAPK_CASCADE, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_DEMETHYLATION, KEGG_ERBB_SIGNALING_PATHWAY, GOBP_COBALAMIN_METABOLIC_PROCESS, GOBP_ERBB_SIGNALING_PATHWAY, CHARAFE_BREAST_CANCER_BASAL_VS_MESENCHYMAL_UP

GO Biological Process (3): glutathione metabolic process (GO:0006749), cobalamin metabolic process (GO:0009235), demethylation (GO:0070988)

GO Molecular Function (10): oxidoreductase activity (GO:0016491), transferase activity, transferring alkyl or aryl (other than methyl) groups (GO:0016765), cobalamin binding (GO:0031419), demethylase activity (GO:0032451), cyanocobalamin reductase (cyanide-eliminating) (NADP+) activity (GO:0033787), protein homodimerization activity (GO:0042803), glutathione binding (GO:0043295), FAD binding (GO:0071949), protein binding (GO:0005515), transferase activity (GO:0016740)

GO Cellular Component (2): cytoplasm (GO:0005737), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Defects in cobalamin (B12) metabolism	2
Cobalamin (Cbl, vitamin B12) transport and metabolism	1
Metabolism of water-soluble vitamins and cofactors	1
Metabolism of vitamins and cofactors	1
Metabolism	1
Defects in vitamin and cofactor metabolism	1
Diseases of metabolism	1
Disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
catalytic activity	3
cellular anatomical structure	2
modified amino acid metabolic process	1
sulfur compound metabolic process	1
tetrapyrrole metabolic process	1
metabolic process	1
transferase activity	1
vitamin binding	1
tetrapyrrole binding	1
heterocyclic compound binding	1
oxidoreductase activity, acting on metal ions, NAD or NADP as acceptor	1
identical protein binding	1
protein dimerization activity	1
anion binding	1
modified amino acid binding	1
oligopeptide binding	1
sulfur compound binding	1
flavin adenine dinucleotide binding	1
binding	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

1348 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MMACHC	LMBRD1	Q9NUN5	972
MMACHC	MMADHC	Q9H3L0	964
MMACHC	MMAA	Q8IVH4	947
MMACHC	MMAB	Q96EY8	947
MMACHC	MMUT	P22033	910
MMACHC	MTR	Q99707	902
MMACHC	DGKE	P52429	780
MMACHC	MTRR	Q9UBK8	773
MMACHC	ABCD4	O14678	735
MMACHC	CFHR5	Q9BXR6	633
MMACHC	CFHR1	Q03591	616
MMACHC	ADAMTS13	Q76LX8	613
MMACHC	CFH	P08603	606
MMACHC	CD320	Q9NPF0	596
MMACHC	MCEE	Q96PE7	593

IntAct

16 interactions, top by confidence:

A	B	Type	Score
TEPSIN	AP4M1	psi-mi:“MI:0914”(association)	0.700
	Mmadhc	psi-mi:“MI:0407”(direct interaction)	0.620
	MMADHC	psi-mi:“MI:0407”(direct interaction)	0.560
MMACHC	CCT6B	psi-mi:“MI:0915”(physical association)	0.500
MTR	MMACHC	psi-mi:“MI:0915”(physical association)	0.470
MMACHC	MTR	psi-mi:“MI:2364”(proximity)	0.470
SELENBP1	CAMKMT	psi-mi:“MI:0914”(association)	0.350
BNIP5	GNPAT	psi-mi:“MI:0914”(association)	0.350
SELENBP1	ZNF24	psi-mi:“MI:0914”(association)	0.350
MMACHC	TCP1	psi-mi:“MI:0914”(association)	0.350
SELENBP1	TRMT5	psi-mi:“MI:0914”(association)	0.350

BioGRID (19): UBE2L3 (Co-fractionation), MMACHC (Affinity Capture-MS), MMACHC (Affinity Capture-RNA), MMACHC (Affinity Capture-MS), MMACHC (Affinity Capture-MS), TCP1 (Affinity Capture-MS), CCT2 (Affinity Capture-MS), CCT7 (Affinity Capture-MS), CCT4 (Affinity Capture-MS), MMACHC (Affinity Capture-MS), CCT6B (Affinity Capture-MS), MMACHC (Affinity Capture-MS), CCT3 (Affinity Capture-MS), PDCL (Affinity Capture-MS), CCT6A (Affinity Capture-MS)

ESM2 similar proteins: A0A0B5AC19, A1VN15, A2C538, A2CBW9, A2CCP5, A4XT72, A5GIZ3, A5GVQ6, A8IC17, A9KC01, A9NA93, O52512, O89748, P03513, P04873, P08463, P14961, P45944, P52132, P72848, P77206, P84786, Q00124, Q02189, Q02190, Q0ICV5, Q16BB4, Q1GLD5, Q1I6K3, Q3AMK3, Q3AUU4, Q3AWA8, Q46IM1, Q51320, Q5N3S5, Q5N5A3, Q6E0W8, Q6LLK0, Q7NEK3, Q7U4M7

Diamond homologs: Q5E9C8, Q5RFU5, Q5ZL21, Q7Z144, Q9CZD0, Q9Y4U1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	58
Likely pathogenic	49
Uncertain significance	264
Likely benign	195
Benign	22

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1076507	NM_015506.3(MMACHC):c.449T>A (p.Ile150Lys)	Pathogenic
1076669	NM_015506.3(MMACHC):c.123dup (p.Pro42fs)	Pathogenic
1252060	NM_015506.3(MMACHC):c.352C>T (p.Gln118Ter)	Pathogenic
1334896	NM_015506.3(MMACHC):c.187del (p.Leu63fs)	Pathogenic
1368644	NM_015506.3(MMACHC):c.315C>A (p.Tyr105Ter)	Pathogenic
1421	NM_015506.3(MMACHC):c.271dup (p.Arg91fs)	Pathogenic
1423	NM_015506.3(MMACHC):c.394C>T (p.Arg132Ter)	Pathogenic
1424	NM_015506.3(MMACHC):c.331C>T (p.Arg111Ter)	Pathogenic
1446343	NM_015506.3(MMACHC):c.419G>A (p.Trp140Ter)	Pathogenic
1453962	NC_000001.10:g.(?45965995)(45966095_?)del	Pathogenic
1454386	NM_015506.3(MMACHC):c.534del (p.Lys178fs)	Pathogenic
1459897	NC_000001.10:g.(?45974458)(45974897_?)del	Pathogenic
161117	NM_015506.3(MMACHC):c.276G>T (p.Glu92Asp)	Pathogenic
161119	NM_015506.3(MMACHC):c.464G>A (p.Gly155Glu)	Pathogenic
1938082	NM_015506.3(MMACHC):c.151_152del (p.Leu51fs)	Pathogenic
2024522	NM_015506.3(MMACHC):c.81+1G>T	Pathogenic
2027786	NM_015506.3(MMACHC):c.477_478insCATCCGAGGGGTAGTGCTGCTGCCAGGGATAGAGGTGCCAGATCTGCCACCCAGAAAACCTCATGACTGTGTACCTACAAGAGCTGAC (p.Ile160delinsHisProArgGlySerAlaAlaAlaArgAspArgGlyAlaArgSerAlaThrGlnLysThrSerTer)	Pathogenic
203823	NM_015506.3(MMACHC):c.3G>A (p.Met1Ile)	Pathogenic
203825	NM_015506.3(MMACHC):c.217C>T (p.Arg73Ter)	Pathogenic
203827	NM_015506.3(MMACHC):c.420G>A (p.Trp140Ter)	Pathogenic
203834	NM_015506.3(MMACHC):c.445_446del (p.Cys149fs)	Pathogenic
203835	NM_015506.3(MMACHC):c.328_331del (p.Asn110fs)	Pathogenic
2068815	NM_015506.3(MMACHC):c.433del (p.Ile145fs)	Pathogenic
2130931	NM_015506.3(MMACHC):c.81+2T>C	Pathogenic
2202756	NM_015506.3(MMACHC):c.14_24del (p.Val5fs)	Pathogenic
2504060	NM_015506.3(MMACHC):c.321_329delinsACACC (p.Asn110fs)	Pathogenic
2676630	NM_015506.3(MMACHC):c.228_231del (p.Asp77fs)	Pathogenic
2717233	NM_015506.3(MMACHC):c.93C>A (p.Tyr31Ter)	Pathogenic
2725295	NM_015506.3(MMACHC):c.1A>T (p.Met1Leu)	Pathogenic
2733897	NM_015506.3(MMACHC):c.126_141del (p.Leu43fs)	Pathogenic

SpliceAI

542 predictions. Top by Δscore:

Variant	Effect	Δscore
1:45507548:GAG:G	donor_gain	1.0000
1:45507548:GAGGT:G	donor_loss	1.0000
1:45507549:AGG:A	donor_loss	1.0000
1:45507550:GGT:G	donor_loss	1.0000
1:45507552:T:A	donor_loss	1.0000
1:45508202:A:AG	acceptor_gain	1.0000
1:45508202:ACT:A	acceptor_gain	1.0000
1:45508203:C:G	acceptor_gain	1.0000
1:45508204:T:A	acceptor_gain	1.0000
1:45508207:TCCA:T	acceptor_loss	1.0000
1:45508208:CCA:C	acceptor_loss	1.0000
1:45508208:CCAG:C	acceptor_gain	1.0000
1:45508209:CAG:C	acceptor_gain	1.0000
1:45508210:A:AG	acceptor_gain	1.0000
1:45508210:AGA:A	acceptor_gain	1.0000
1:45508211:G:C	acceptor_gain	1.0000
1:45508211:G:GA	acceptor_gain	1.0000
1:45508211:GA:G	acceptor_gain	1.0000
1:45508211:GAGC:G	acceptor_gain	1.0000
1:45508211:GAGCC:G	acceptor_gain	1.0000
1:45508363:AG:A	donor_loss	1.0000
1:45508364:GGT:G	donor_loss	1.0000
1:45508366:T:G	donor_loss	1.0000
1:45511411:CACA:C	acceptor_gain	1.0000
1:45511412:ACA:A	acceptor_gain	1.0000
1:45511413:CA:C	acceptor_gain	1.0000
1:45511413:CAC:C	acceptor_gain	1.0000
1:45511414:ACT:A	acceptor_loss	1.0000
1:45511415:C:CC	acceptor_gain	1.0000
1:45500378:C:G	donor_gain	0.9900

AlphaMissense

1806 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:45507434:A:C	S54R	0.995
1:45507436:C:A	S54R	0.995
1:45507436:C:G	S54R	0.995
1:45508838:T:C	F158L	0.993
1:45508840:T:A	F158L	0.993
1:45508840:T:G	F158L	0.993
1:45508297:C:A	A121D	0.992
1:45508835:T:A	W157R	0.991
1:45508835:T:C	W157R	0.991
1:45508813:C:G	C149W	0.990
1:45507449:T:C	F59L	0.989
1:45507451:T:A	F59L	0.989
1:45507451:T:G	F59L	0.989
1:45508952:T:C	F196L	0.987
1:45508954:C:A	F196L	0.987
1:45508954:C:G	F196L	0.987
1:45508811:T:C	C149R	0.985
1:45509030:T:G	Y222D	0.984
1:45508305:G:C	A124P	0.982
1:45508812:G:A	C149Y	0.982
1:45508830:G:A	G155E	0.982
1:45508839:T:C	F158S	0.982
1:45508306:C:A	A124D	0.981
1:45507518:T:C	C82R	0.980
1:45508294:C:A	A120E	0.980
1:45508315:C:A	A127D	0.980
1:45509033:T:C	F223L	0.980
1:45509035:C:A	F223L	0.980
1:45509035:C:G	F223L	0.980
1:45508819:C:A	H151Q	0.979

dbSNP variants (sampled 300 via entrez): RS1000037450 (1:45504287 G>C), RS1000250797 (1:45507222 A>G), RS1000355237 (1:45510918 T>C), RS1000410685 (1:45510632 C>A), RS1000688178 (1:45512743 C>G,T), RS1000976572 (1:45506801 C>T), RS1001148146 (1:45500812 C>T), RS1001170788 (1:45513345 G>A), RS1001194334 (1:45512301 G>A,C), RS1001596498 (1:45500782 T>G), RS1001626236 (1:45506134 G>A), RS1001774683 (1:45511999 G>A,T), RS1001918843 (1:45513080 A>C), RS1001973766 (1:45511631 C>A), RS1002236397 (1:45507805 T>C)

Disease associations

OMIM: gene MIM:609831 | disease phenotypes: MIM:277400, MIM:251000, MIM:277410

GenCC curated gene-disease

Disease	Classification	Inheritance
methylmalonic aciduria and homocystinuria type cblC	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
methylmalonic aciduria and homocystinuria type cblC	Definitive	AR

Mondo (7): methylmalonic aciduria and homocystinuria type cblC (MONDO:0010184), atypical hemolytic-uremic syndrome (MONDO:0016244), methylmalonic aciduria and homocystinuria (MONDO:0016826), methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency (MONDO:0009612), methylmalonic aciduria and homocystinuria type cblD (MONDO:0010185), homocystinuria (MONDO:0004737), inherited retinal dystrophy (MONDO:0019118)

Orphanet (7): Methylmalonic acidemia with homocystinuria (Orphanet:26), Methylmalonic acidemia with homocystinuria, type cblC (Orphanet:79282), Atypical hemolytic uremic syndrome (Orphanet:2134), Vitamin B12-unresponsive methylmalonic acidemia (Orphanet:27), Homocystinuria without methylmalonic aciduria (Orphanet:622), Methylmalonic acidemia with homocystinuria, type cblD (Orphanet:79283), OBSOLETE: Inherited retinal disorder (Orphanet:71862)

HPO phenotypes

113 total (30 of 113 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000083	Renal insufficiency
HP:0000093	Proteinuria
HP:0000112	Nephropathy
HP:0000206	Glossitis
HP:0000238	Hydrocephalus
HP:0000252	Microcephaly
HP:0000276	Long face
HP:0000319	Smooth philtrum
HP:0000348	High forehead
HP:0000369	Low-set ears
HP:0000400	Macrotia
HP:0000505	Visual impairment
HP:0000546	Retinal degeneration
HP:0000580	Pigmentary retinopathy
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000707	Abnormality of the nervous system
HP:0000708	Atypical behavior
HP:0000709	Psychosis
HP:0000726	Dementia
HP:0000751	Personality changes
HP:0000790	Hematuria
HP:0000952	Jaundice
HP:0000980	Pallor
HP:0001116	Macular pseudocoloboma
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia

GWAS associations

16 associations (top):

Study	Trait	p-value
GCST002087_8	Homocysteine levels	2.000000e-09
GCST005950_15	Body mass index x sex x age interaction (4df test)	2.000000e-10
GCST005951_56	Body mass index	1.000000e-06
GCST005952_8	Body mass index (age>50)	9.000000e-12
GCST005954_4	Body mass index x age interaction	2.000000e-07
GCST006990_2	Cerebrospinal AB1-42 levels in Alzheimer’s disease dementia	3.000000e-07
GCST007320_18	Alzheimer’s disease or family history of Alzheimer’s disease	7.000000e-25
GCST007827_3	Alzheimer’s disease or HDL levels (pleiotropy)	1.000000e-97
GCST007827_5	Alzheimer’s disease or HDL levels (pleiotropy)	7.000000e-74
GCST007827_6	Alzheimer’s disease or HDL levels (pleiotropy)	7.000000e-54
GCST007827_7	Alzheimer’s disease or HDL levels (pleiotropy)	5.000000e-50
GCST007827_8	Alzheimer’s disease or HDL levels (pleiotropy)	3.000000e-36
GCST007848_3	LDL cholesterol	6.000000e-30
GCST008152_195	Weight	9.000000e-06
GCST009496_8	Alzheimer’s disease (onset between ages 58 and 79)	3.000000e-11
GCST010243_209	Apolipoprotein B levels	0.000000e+00

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0004578	homocysteine measurement
EFO:0004340	body mass index
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0004670	beta-amyloid 1-42 measurement
EFO:0009268	family history of Alzheimer’s disease
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004338	body weight
EFO:0004615	apolipoprotein B measurement

MeSH disease descriptors (6)

Descriptor	Name	Tree numbers
D065766	Atypical Hemolytic Uremic Syndrome	C12.050.351.968.419.936.463.500; C12.200.777.419.936.463.500; C12.950.419.936.463.500; C15.378.050.141.610.500; C15.378.140.855.925.500.500; C15.378.243.937.925.500.500
D006712	Homocystinuria	C10.228.140.163.100.365; C16.320.565.100.480.500; C16.320.565.189.365; C17.300.428; C18.452.132.100.365; C18.452.648.100.480.500; C18.452.648.189.365
D058499	Retinal Dystrophies	C11.768.585.658
C564743	Methylmalonic Aciduria and Homocystinuria, CblD Type (supp.)
C565390	Methylmalonic Aciduria due to Methylmalonyl-CoA Mutase Deficiency (supp.)
C537359	Methylmalonic acidemia with homocystinuria (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	3
(+)-JQ1 compound	decreases expression	3
Acetaminophen	decreases expression	2
Tobacco Smoke Pollution	decreases expression	2
Cyclosporine	decreases expression	2
Aflatoxin B1	decreases expression, decreases methylation	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
aminomethylphosphonic acid (AMPA)	decreases expression	1
dicrotophos	increases expression	1
pirinixic acid	increases expression, affects binding, increases activity	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
isobutyl alcohol	affects cotreatment, decreases expression, increases abundance	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
cylindrospermopsin	increases expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	decreases expression	1
abrine	decreases expression	1
NSC 689534	affects binding, decreases expression	1
Sunitinib	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Arsenic	increases abundance, increases expression	1
Benzo(a)pyrene	decreases expression	1
Copper	affects binding, decreases expression	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	decreases expression	1
Gasoline	affects cotreatment, decreases expression, increases abundance	1
Hydroxocobalamin	affects binding	1

Cellosaurus cell lines

57 cell lines: 51 finite cell line, 4 cancer cell line, 2 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_B3WE	WG1070	Finite cell line
CVCL_B3WF	WG1127	Finite cell line
CVCL_B3WG	WG1129	Finite cell line
CVCL_B3WH	WG1135	Finite cell line
CVCL_B3WI	WG1391	Finite cell line
CVCL_B3WJ	WG1404	Finite cell line
CVCL_B3WK	WG1481	Finite cell line
CVCL_B3WL	WG1496	Finite cell line
CVCL_B3WQ	WG1692	Finite cell line
CVCL_B3WR	WG2339	Finite cell line

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02574403	PHASE4	COMPLETED	Study Assessing an Algorithm-based Strategy of Eculizumab Discontinuation in Children and Adults With aHUS
NCT07308574	PHASE4	RECRUITING	Post-Marketing Clinical Study of Ravulizumab in Participants With Clinical aHUS
NCT02949128	PHASE3	COMPLETED	Study of ALXN1210 in Complement Inhibitor Treatment-Naïve Adult and Adolescent Participants With Atypical Hemolytic Uremic Syndrome (aHUS)
NCT03131219	PHASE3	COMPLETED	Study of Ravulizumab in Children and Adolescents With Atypical Hemolytic Uremic Syndrome (aHUS)
NCT03205995	PHASE3	TERMINATED	Safety and Efficacy Study of OMS721 in Patients With Atypical Hemolytic Uremic Syndrome
NCT04861259	PHASE3	ACTIVE_NOT_RECRUITING	A Study Evaluating the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Crovalimab in Adult and Adolescent Participants With Atypical Hemolytic Uremic Syndrome (aHUS)
NCT04889430	PHASE3	COMPLETED	Efficacy and Safety of Iptacopan (LNP023) in Adult Patients With Atypical Hemolytic Uremic Syndrome Naive to Complement Inhibitor Therapy
NCT04958265	PHASE3	ACTIVE_NOT_RECRUITING	A Study Evaluating the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Crovalimab in Pediatric Participants With Atypical Hemolytic Uremic Syndrome (aHUS)
NCT05795140	PHASE3	RECRUITING	Evaluate Long-term Safety, Tolerability and Efficacy of Iptacopan in Study Participants With aHUS
NCT05935215	PHASE3	RECRUITING	Efficacy and Safety of Switching From Anti-C5 Antibody Treatment to Iptacopan Treatment in Study Participants With Atypical Hemolytic Uremic Syndrome (aHUS)
NCT06247085	PHASE3	RECRUITING	A Study to Investigate Efficacy and Safety of Pegtibatinase Compared With Placebo in Participants ≥12 to ≤65 Years of Age With Classical Homocystinuria (HCU) Due to Cystathionine Beta Synthase Deficiency Receiving Standard of Care Treatment
NCT06431893	PHASE3	ENROLLING_BY_INVITATION	A Long-term Extension Study to Assess the Long-term Safety and Efficacy of Pegtibatinase Treatment in Participants ≥5 to ≤65 Years of Age With Classical Homocystinuria (HCU) (ENSEMBLE)
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT00838513	PHASE2	COMPLETED	Open Label Controlled Trial of Eculizumab in Adult Patients With Plasma Therapy-sensitive Atypical Hemolytic Uremic Syndrome (aHUS)
NCT00844428	PHASE2	COMPLETED	Open Label Controlled Trial of Eculizumab in Adolescent Patients With Plasma Therapy-Sensitive aHUS
NCT00844545	PHASE2	COMPLETED	Open Label Controlled Trial of Eculizumab in Adult Patients With Plasma Therapy-Resistant aHUS
NCT00844844	PHASE2	COMPLETED	Open Label Controlled Trial of Eculizumab in Adolescent Patients With Plasma Therapy-Resistant aHUS
NCT01193348	PHASE2	COMPLETED	An Open-Label, Multi-Center Clinical Trial of Eculizumab in Pediatric Patients With Atypical Hemolytic-Uremic Syndrome
NCT01194973	PHASE2	COMPLETED	An Open-label, Multi-center Clinical Trial of Eculizumab in Adult Patients With Atypical Hemolytic-uremic Syndrome
NCT01757431	PHASE2	COMPLETED	The Safety and Efficacy of Eculizumab in Japanese Patients With Atypical Hemolytic Uremic Syndrome (aHUS)
NCT02464891	PHASE2	TERMINATED	Complement Inhibition in aHUS Dialysis Patients
NCT03303313	PHASE2	WITHDRAWN	A Study of an Investigational Drug, Cemdisiran (ALN-CC5), in Patients With Atypical Hemolytic Uremic Syndrome
NCT03518203	PHASE2	COMPLETED	Eculizumab to Treat Thrombotic Microangiopathy/Atypical Hemolytic Uremic Syndrome -Associated Multiple Organ Dysfunction Syndrome in Hematopoietic Stem Cell Transplant Recipients
NCT03999840	PHASE2	WITHDRAWN	Eculizumab to Cemdisiran Switch in aHUS
NCT04725812	PHASE2	TERMINATED	Complement Regulation to Undo Systemic Harm in Preeclampsia
NCT00483314	PHASE2	COMPLETED	Homocystinuria: Treatment With N-Acetylcysteine
NCT02404337	PHASE2	COMPLETED	Betaine METABOLISM OF PATIENTS With Homocystinuria
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT05462132	PHASE1	COMPLETED	Safety, Tolerability and Pharmacodynamics of SYNB1353 in Healthy Adult Volunteers
NCT05902962	PHASE1	COMPLETED	SAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects
NCT06319872	PHASE1	RECRUITING	The Effects of Disulfiram (Antabuse®) on Visual Acuity in Patients With Retinal Degeneration
NCT06455826	PHASE1	COMPLETED	MAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects (Wallaby)
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns
NCT01522170	Not specified	TERMINATED	aHUS Observational Long Term Follow-Up
NCT01522183	Not specified	RECRUITING	Atypical Hemolytic-Uremic Syndrome (aHUS) Registry
NCT01755429	Not specified	COMPLETED	To Characterize the Safety and Tolerability of Eculizumab in Two Japanese aHUS Patients
NCT01770951	Not specified	COMPLETED	A Retrospective, Observational, Non-interventional Trial to Assess Eculizumab Treatment Effect in Patients With Atypical Hemolytic Uremic Syndrome (aHUS)