PANTHER is a database for classifying protein families and subfamilies based on function. It consists of two main components: PANTHER/LIB, which contains multiple sequence alignments, HMMs, and family trees, and PANTHER/X, an ontology for summarizing and navigating molecular functions and biological processes. PANTHER is used to analyze protein families and subfamilies, characterize sequence and functional divergence, and rank missense SNPs based on their likelihood of affecting protein function. The database includes over 2200 protein families and 30,000 subfamilies, with each family represented as a tree, multiple sequence alignment, and HMM. Subfamilies are defined by biologists and associated with PANTHER/X terms. PANTHER/X provides a simplified ontology for high-level analysis of protein functions. The database also includes HMMs for predicting the functional impact of amino acid substitutions. PANTHER has been used to analyze the functional diversity of protein families, classify genes based on function, and predict the effect of SNPs on protein function. The results show that PANTHER/X provides a more even distribution of function associations across categories compared to GO. The HMMs in PANTHER are used to score the likelihood of amino acid substitutions and to predict the functional impact of SNPs. The results indicate that position-specific scores are more effective than substitution matrices like BLOSUM62 for predicting the functional impact of SNPs. PANTHER is a comprehensive resource for protein family and subfamily classification, with applications in genomics, proteomics, and functional genomics.PANTHER is a database for classifying protein families and subfamilies based on function. It consists of two main components: PANTHER/LIB, which contains multiple sequence alignments, HMMs, and family trees, and PANTHER/X, an ontology for summarizing and navigating molecular functions and biological processes. PANTHER is used to analyze protein families and subfamilies, characterize sequence and functional divergence, and rank missense SNPs based on their likelihood of affecting protein function. The database includes over 2200 protein families and 30,000 subfamilies, with each family represented as a tree, multiple sequence alignment, and HMM. Subfamilies are defined by biologists and associated with PANTHER/X terms. PANTHER/X provides a simplified ontology for high-level analysis of protein functions. The database also includes HMMs for predicting the functional impact of amino acid substitutions. PANTHER has been used to analyze the functional diversity of protein families, classify genes based on function, and predict the effect of SNPs on protein function. The results show that PANTHER/X provides a more even distribution of function associations across categories compared to GO. The HMMs in PANTHER are used to score the likelihood of amino acid substitutions and to predict the functional impact of SNPs. The results indicate that position-specific scores are more effective than substitution matrices like BLOSUM62 for predicting the functional impact of SNPs. PANTHER is a comprehensive resource for protein family and subfamily classification, with applications in genomics, proteomics, and functional genomics.