Q5: How do I report issues or suggest improvements?

Q1: How do I use Gene Lookup?

Gene Lookup allows you to search by gene name, genomic region, disease name, or phenotype. You can also apply advanced filters for inheritance mode, data source, constraint scores, ClinGen classification, or other structured fields.

Example use cases:

Example #1	Search for a specific gene like BRCA1
Example #2	Search for all genes associated with cardiomyopathy
Example #3	Search for all disease-associated genes in a genomic region

Q2: What data sources are included?

Gene Lookup aggregates gene-disease association data from the following sources:

OMIM — Online Mendelian Inheritance in Man
ClinGen — Gene-disease validity classifications
GenCC — Gene Curation Coalition
PanelApp UK — Genomics England PanelApp
PanelApp Australia — Australian Genomics PanelApp
DECIPHER — DDG2P gene-disease associations
ClinVar — Pathogenic/likely pathogenic variant annotations
GWAS Catalog — GWAS hits for MONDO rare-disease phenotypes
Fridman et al. 2025 — Autosomal recessive gene-disease associations
gnomAD constraint metrics — pLI, LOEUF, and Missense O/E from gnomAD v4

Q3: What are the constraint scores?

Constraint scores from gnomAD v4 reflect how tolerant a gene is to different types of variation:

pLI — Probability of loss-of-function intolerance. Values close to 1 indicate the gene is highly intolerant to loss-of-function variants.
LOEUF — Loss-of-function observed/expected upper bound fraction. Lower values indicate greater constraint. A threshold of ≤0.35 is commonly used to identify constrained genes.
Missense O/E — Missense observed/expected ratio. Lower values suggest the gene is intolerant to missense variation.

Q4: What is the phenotype summary?

The summary is created by aggregating phenotype descriptions from the data sources listed in Q2 and feeding them into a large language model (Gemini Flash) to produce a concise summary.

Q5: How do I report issues or suggest improvements?

Open an issue on the GitHub repository or email weisburd@broadinstitute.org